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Sample records for developed parasitic perfusion

  1. Malaria parasite development in mosquitoes.

    PubMed

    Beier, J C

    1998-01-01

    Mosquitoes of the genus Anopheles transmit malaria parasites to humans. Anopheles mosquito species vary in their vector potential because of environmental conditions and factors affecting their abundance, blood-feeding behavior, survival, and ability to support malaria parasite development. In the complex life cycle of the parasite in female mosquitoes, a process termed sporogony, mosquitoes acquire gametocyte-stage parasites from blood-feeding on an infected host. The parasites carry out fertilization in the midgut, transform to ookinetes, then oocysts, which produce sporozoites. Sporozoites invade the salivary glands and are transmitted when the mosquito feeds on another host. Most individual mosquitoes that ingest gametocytes do not support development to the sporozoite stage. Bottle-necks occur at every stage of the cycle in the mosquito. Powerful new techniques and approaches exist for evaluating malaria parasite development and for identifying mechanisms regulating malaria parasite-vector interactions. This review focuses on those interactions that are important for the development of new approaches for evaluating and blocking transmission in nature.

  2. Developing a Benchmarking Process in Perfusion: A Report of the Perfusion Downunder Collaboration

    PubMed Central

    Baker, Robert A.; Newland, Richard F.; Fenton, Carmel; McDonald, Michael; Willcox, Timothy W.; Merry, Alan F.

    2012-01-01

    Abstract: Improving and understanding clinical practice is an appropriate goal for the perfusion community. The Perfusion Downunder Collaboration has established a multi-center perfusion focused database aimed at achieving these goals through the development of quantitative quality indicators for clinical improvement through benchmarking. Data were collected using the Perfusion Downunder Collaboration database from procedures performed in eight Australian and New Zealand cardiac centers between March 2007 and February 2011. At the Perfusion Downunder Meeting in 2010, it was agreed by consensus, to report quality indicators (QI) for glucose level, arterial outlet temperature, and pCO2 management during cardiopulmonary bypass. The values chosen for each QI were: blood glucose ≥4 mmol/L and ≤10 mmol/L; arterial outlet temperature ≤37°C; and arterial blood gas pCO2 ≥ 35 and ≤45 mmHg. The QI data were used to derive benchmarks using the Achievable Benchmark of Care (ABC™) methodology to identify the incidence of QIs at the best performing centers. Five thousand four hundred and sixty-five procedures were evaluated to derive QI and benchmark data. The incidence of the blood glucose QI ranged from 37–96% of procedures, with a benchmark value of 90%. The arterial outlet temperature QI occurred in 16–98% of procedures with the benchmark of 94%; while the arterial pCO2 QI occurred in 21–91%, with the benchmark value of 80%. We have derived QIs and benchmark calculations for the management of several key aspects of cardiopulmonary bypass to provide a platform for improving the quality of perfusion practice. PMID:22730861

  3. Parasites

    MedlinePlus

    ... Where to Find Further Information on Parasitic Diseases Public Health Image Library Freedom of Information Act (FOIA) Explore Parasites A-Z Index Parasites Glossary Education and Training Healthy Water Travelers Health Laboratory ... Science Parasites About Parasites Animals ...

  4. Parasitic diarrheal disease: drug development and targets

    PubMed Central

    Azam, Amir; Peerzada, Mudasir N.; Ahmad, Kamal

    2015-01-01

    Diarrhea is the manifestation of gastrointestinal infection and is one of the major causes of mortality and morbidity specifically among the children of less than 5 years age worldwide. Moreover, in recent years there has been a rise in the number of reports of intestinal infections continuously in the industrialized world. These are largely related to waterborne and food borne outbreaks. These occur by the pathogenesis of both prokaryotic and eukaryotic organisms like bacteria and parasites. The parasitic intestinal infection has remained mostly unexplored and under assessed in terms of therapeutic development. The lack of new drugs and the risk of resistance have led us to carry out this review on drug development for parasitic diarrheal diseases. The major focus has been depicted on commercially available drugs, currently synthesized active heterocyclic compounds and unique drug targets, that are vital for the existence and growth of the parasites and can be further exploited for the search of therapeutically active anti-parasitic agents. PMID:26617574

  5. [Views for research development of control of parasitic diseases].

    PubMed

    Zhao, Qin-Ping; Dong, Hui-Fen; Jiang, Ming-Sen

    2013-12-01

    With the social and technological development, new understandings have been emerged for the research development of the control of parasitic diseases. The present review argues that: the traditional point of view for the control of parasitic diseases, eliminating parasites/media, should be updated. For the long-term interests of science and human perspective, biological diversity, including the parasite biodiversity, and ecological environment should be paid much more attention during the control of parasitic diseases. The leading role of society, economy and culture should be fully developed in the control of parasitic diseases with the progress of scientific and technology, to find a final way of sustainable development in the control of parasitic diseases.

  6. Recent developments and future prospects of SPECT myocardial perfusion imaging.

    PubMed

    Zaman, Maseeh Uz; Hashmi, Ibrahim; Fatima, Nosheen

    2010-10-01

    Myocardial perfusion SPECT imaging is the most commonly performed functional imaging for assessment of coronary artery disease. High diagnostic accuracy and incremental prognostic value are the major benefits while suboptimal spatial resolution and significant radiation exposure are the main limitations. Its ability to detect hemodynamic significance of lesions seen on multidetector CT angiogram (MDCTA) has paved the path for a successful marriage between anatomical and functional imaging modalities in the form of hybrid SPECT/MDCTA system. In recent years, there have been enormous efforts by industry and academia to develop new SPECT imaging systems with better sensitivity, resolution, compact design and new reconstruction algorithms with ability to improve image quality and resolution. Furthermore, expected arrival of Tc-99m-labeled deoxyglucose in next few years would further strengthen the role of SPECT in imaging hibernating myocardium. In view of these developments, it seems that SPECT would enjoy its pivotal role in spite of major threat to be replaced by fluorine-18-labeled positron emission tomography perfusion and glucose metabolism imaging agents.

  7. Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps

    PubMed Central

    Fichter, Andreas M.; Ritschl, Lucas M.; Borgmann, Anna; Humbs, Martin; Luppa, Peter B.; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-01-01

    Background Extracorporeal perfusion (ECP) might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps. Methods After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood) were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7. Results ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27%) was even lower than after in vivo perfusion (49%), although not statistically significant (P = 0,083). After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%). Angiographic and histological findings confirmed these observations. Conclusions Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies. PMID:26808996

  8. Endoscopic ICG perfusion imaging for flap transplants: technical development

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Schachenmayr, Hilmar; Ehrhardt, André; Göbel, Werner; Zhorzel, Sven; Betz, Christian Stephan

    2010-02-01

    Objective: Following tumour surgery in the head and neck region, skin flap transplants are usually required to cover the resection area. The purpose of the development was to provide a simple and reliable means to assess whether the transplanted flap is sufficiently perfused. Methods: Fluorescence of intravenously injected Indocyanine green (ICG) was detected with a slightly modified 3-chip CCD camera. Appropriately coated optical filters allow for excitation of ICG with NIR light and detection of NIR ICGfluorescence with the blue channel of the camera. In addition, low intensities of white light can be transmitted to allow for simultaneous display of a remission image in the green and red channels of the camera. Further processing was performed with a LabVIEW program. Results: A satisfactory white light image (red, green and blue display (RGB)) could be calculated from the remission images recorded with the green and red channels of the camera via a look-up table. The look-up table was programmed to provide an optimized blue intensity value for each combination of red and green values. This was generated using a reference image. Implementation of image tracking and intensity measurements in regions of interest (ROIs) in the images is useful to reliably monitor perfusion kinetics of flap and adjacent normal tissue.

  9. DEVELOPMENT OF APTAMERS TO WATERBORNE PARASITES

    EPA Science Inventory

    The Safe Drinking Water Act Amendment of 1996 mandates that the U. S. Environmental Protection Agency (EPA) evaluate public health risks associated with drinking water contaminants to include waterborne parasites, such as Cryptosporidium and Giardia. Additionally, the Agency est...

  10. DEVELOPMENT OF APTAMERS TO WATERBORNE PARASITES

    EPA Science Inventory

    The Safe Drinking Water Act Amendment of 1996 mandates that the U. S. Environmental Protection Agency (EPA) evaluate public health risks associated with drinking water contaminants to include waterborne parasites, such as Cryptosporidium and Giardia. Additionally, the Agency est...

  11. Nematode parasites of animals are more prone to develop xenobiotic resistance than nematode parasites of plants.

    PubMed

    Silvestre, A; Cabaret, J

    2004-06-01

    In this paper, we concentrate on a comparison of plant and animal-parasitic nematodes, to gain insight into the factors that influence the acquisition of the drug resistance by nematodes. Comparing nematode parasite of domestic animals and cultivated plants, it appears that drug resistance threatens only domestic animal production. Does the paucity of report on nematicide field resistance reflect reality or, is nematicide resistance bypassed by other management practices, specific to cultivated plants (i.e. agricultural control)? First, it seems that selection pressure by treatments in plants is not as efficient as selection pressure in ruminants. Agronomic practices (i.e. sanitation, early planting, usage of nematodes resistant cultivar and crop rotation) are frequently used to control parasitic-plant nematodes. Although the efficiency of such measures is generally moderate to high, integrated approaches are developing successfully in parasitic-plant nematode models. Secondly, the majority of anthelmintic resistance cases recorded in animal-parasitic nematodes concern drug families that are not used in plant-parasitic nematodes control (i.e. benzimidazoles, avermectines and levamisole). Thirdly, particular life traits of parasitic-plant nematodes (low to moderate fecundity and reproductive strategy) are expected to reduce probability of appearance and transmission of drug resistance genes. It has been demonstrated that, for a large number of nematodes such as Meloidogyne spp., the mode of reproduction by mitotic parthenogenesis reduced genetic diversity of populations which may prevent a rapid drug resistance development. In conclusion, anthelmintic resistance develops in nematode parasite of animals as a consequence of an efficient selection pressure. Early detection of anthelmintic resistance is then crucial: it is not possible to avoid it, but only to delay its development in farm animal industry.

  12. Alternative parasite development in transmission strategies: how time flies!

    PubMed

    Badets, M; Morrison, C; Verneau, O

    2010-10-01

    Among parasitic platyhelminths with complex life cycles, it has been well documented that transmission opportunities are the main forces shaping the diversity of life-history traits and parasite developmental strategies. While deviations in the development pathway usually involve shortening of life cycles, their extension may also occur following perception of remaining time by parasites. Polystoma gallieni, the monogenean parasite of Hyla meridionalis, is able to trigger two alternative developmental strategies depending on the physiological stage of the tadpoles upon which larvae attach. The distribution and reproductive outputs of both resulting phenotypes were surveyed to address questions about the dynamics of transmission in natural environments. Because modifications in the completion of life cycles can have drawbacks which may perturb the dynamic equilibrium of the resulting host-parasite systems, experimental infestations were also performed to assess parasite-parasite interactions. Our results suggest that the bladder adult phenotype, which involves transmission between frogs and tadpoles, is supplied secondarily by the branchial phenotype which involves transmission between tadpoles and metamorphs. They also support the occurrence of finely tuned trade-offs between hosts and parasites and highlight positive trends behind the extension of direct life cycles, in which host-derived signals account for the remaining time to achieve parasitic transmission.

  13. [Challenge of developing anti-parasite vaccines in the tropics].

    PubMed

    Rogier, C

    2007-08-01

    Much effort has been devoted to developing anti-parasite vaccines. The main obstacles to overcome involve problems in cultivating parasites, variability in antigens of cultivated parasites, insufficient immune responses that do not provide full protection, lack of animal models and difficulty in evaluating immune protection acquired naturally or after vaccination in populations living in endemic areas. Numerous clinical trials have been conducted and several parasite antigens, in particular against malaria, have been tested in endemic areas. Up to now no candidate vaccine has shown sufficient, long-term efficacy to justify its inclusion in public health program. However trials using anti-parasite vaccination under both experimental and field conditions clearly demonstrate that a certain level of clinical immunity against malaria, bilharziasis, and leishmaniasis.

  14. Leishmania development in sand flies: parasite-vector interactions overview.

    PubMed

    Dostálová, Anna; Volf, Petr

    2012-12-03

    Leishmaniases are vector-borne parasitic diseases with 0.9 - 1.4 million new human cases each year worldwide. In the vectorial part of the life-cycle, Leishmania development is confined to the digestive tract. During the first few days after blood feeding, natural barriers to Leishmania development include secreted proteolytic enzymes, the peritrophic matrix surrounding the ingested blood meal and sand fly immune reactions. As the blood digestion proceeds, parasites need to bind to the midgut epithelium to avoid being excreted with the blood remnant. This binding is strictly stage-dependent as it is a property of nectomonad and leptomonad forms only. While the attachment in specific vectors (P. papatasi, P. duboscqi and P. sergenti) involves lipophosphoglycan (LPG), this Leishmania molecule is not required for parasite attachment in other sand fly species experimentally permissive for various Leishmania. During late-stage infections, large numbers of parasites accumulate in the anterior midgut and produce filamentous proteophosphoglycan creating a gel-like plug physically obstructing the gut. The parasites attached to the stomodeal valve cause damage to the chitin lining and epithelial cells of the valve, interfering with its function and facilitating reflux of parasites from the midgut. Transformation to metacyclic stages highly infective for the vertebrate host is the other prerequisite for effective transmission. Here, we review the current state of knowledge of molecular interactions occurring in all these distinct phases of parasite colonization of the sand fly gut, highlighting recent discoveries in the field.

  15. The development of malaria parasites in the mosquito midgut

    PubMed Central

    Bennink, Sandra; Kiesow, Meike J.

    2016-01-01

    Summary The mosquito midgut stages of malaria parasites are crucial for establishing an infection in the insect vector and to thus ensure further spread of the pathogen. Parasite development in the midgut starts with the activation of the intraerythrocytic gametocytes immediately after take‐up and ends with traversal of the midgut epithelium by the invasive ookinetes less than 24 h later. During this time period, the plasmodia undergo two processes of stage conversion, from gametocytes to gametes and from zygotes to ookinetes, both accompanied by dramatic morphological changes. Further, gamete formation requires parasite egress from the enveloping erythrocytes, rendering them vulnerable to the aggressive factors of the insect gut, like components of the human blood meal. The mosquito midgut stages of malaria parasites are unprecedented objects to study a variety of cell biological aspects, including signal perception, cell conversion, parasite/host co‐adaptation and immune evasion. This review highlights recent insights into the molecules involved in gametocyte activation and gamete formation as well as in zygote‐to‐ookinete conversion and ookinete midgut exit; it further discusses factors that can harm the extracellular midgut stages as well as the measures of the parasites to protect themselves from any damage. PMID:27111866

  16. Experimental platynosomosis: Characterization of parasite development in the mouse model.

    PubMed

    Pinto, Hudson A; Mati, Vitor L T; Melo, Alan L

    2015-06-30

    equivalent to those reported for parasites from natural hosts (cats, birds and nonhuman primates). The results obtained provide new insights into the biology of P. illiciens, and the kinetics of the parasite development of this species is presented here for the first time. The potential use of mice as an experimental model for P. illiciens is presented and the implications of the results obtained in that model for feline platynosomosis are briefly discussed.

  17. Development and application of a high-throughput platform for perfusion-based cell culture processes.

    PubMed

    Villiger-Oberbek, Agata; Yang, Yang; Zhou, Weichang; Yang, Jianguo

    2015-10-20

    A high-throughput (HT) cell culture model has been established for the support of perfusion-based cell culture processes operating at high cell densities. To mimic perfusion, the developed platform takes advantage of shake tubes and operates them in a batch-refeed mode with daily medium exchange to supply the cultures with nutrients and remove toxic byproducts. By adjusting the shaking parameters, such as the speed and setting angle, we have adapted the shake tubes to a semi-continuous production of a recombinant enzyme in a perfusion-like mode. We have demonstrated that the developed model can be used to select clones and cell culture media ahead of process optimization studies in bioreactors and confirmed the applicability of shake tubes to a perfusion-like cell culture reaching ∼50E6 viable cells/mL. Furthermore, through regular cell mass removal and periodic medium exchange we have successfully maintained satellite cultures of bench-top perfusion bioreactors, achieving a sustainable cell culture performance at ≥30E6 viable cells/mL and viabilities >80% for over 58 days. The established HT model is a unique and powerful tool that can be used for the development and screening of media formulations, or for testing selected process parameters during both process optimization and manufacturing support campaigns.

  18. A historical perspective on the development of modern concepts of tissue perfusion: prehistory to the twentieth century.

    PubMed

    Ashby, Nathan; Squiers, Joshua

    2014-09-01

    The historical development of the concept of perfusion is traced, with particular focus on the development of the modern clinical concepts of perfusion through the fields of anatomy, physiology, and biochemistry. This article reviews many of the significant contributors to the changing ideas of perfusion up through the twentieth century that have influenced the modern physiologic circulatory and metabolic models. The developments outlined have provided the modern model of perfusion, linking the cardiopulmonary circulation, tissue oxygen utilization and carbon dioxide production, food intake, tissue waste production and elimination, and ultimately the production and utilization of ATP in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Chemical Factors in Development and Transmission of Human Parasites.

    DTIC Science & Technology

    PARASITES, *PREVENTIVE MEDICINE, *BIOCIDES, *REPELLENTS, HORMONES, TABLES(DATA), SCHISTOSOMA MANSONI , BRAZIL, PARASITIC DISEASES, DISEASE VECTORS, INSECT REPELLENTS, CHAGAS DISEASE, TRYPANOSOMA CRUZI.

  20. Leishmania vaccine development: exploiting the host-vector-parasite interface.

    PubMed

    Reed, S G; Coler, R N; Mondal, D; Kamhawi, S; Valenzuela, J G

    2016-01-01

    Visceral leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as vaccines. This review discusses the notion that a combination vaccine including Leishmania and vector salivary antigens may improve vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of leishmaniasis vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective vaccines against leishmaniasis can be developed.

  1. Seed parasitism redirects ovule development in Douglas fir

    PubMed Central

    von Aderkas, Patrick; Rouault, Gaëlle; Wagner, Rebecca; Rohr, René; Roques, Alain

    2005-01-01

    Many parasitic species of insects complete their entire development in seeds. They feed off storage reserves within the ovule. These reserves only normally accumulate in fertilized ovules. Consequently, female insects that oviposit their eggs directly into the plant ovule need to be able to select correctly, as unfertilized ovules of conifers normally become so-called empty seed. We provide clear evidence that in conifers, seed-parasitizing insects do not need to discriminate between fertilized and unfertilized plant ovules when ovipositing their eggs. A host-specific insect, the chalcid Megastigmus spermotrophus Wachtl (Hymenoptera: Torymidae), lays its eggs in ovules of Douglas fir (Pseudotsuga menziesii (Mirbel) Franco) before fertilization has taken place in the plant. Oviposition not only prevents the expected degeneration and death of unfertilized ovules, but it induces energy reserve accumulation. Ovules that would otherwise develop as empty seed are redirected in their development by the insect to provide food for the developing larvae. Instead of the insect exploiting normal events during seed development, the insect manipulates seed development for its own reproductive advantage. PMID:16011924

  2. Supportive development of functional tissues for biomedical research using the MINUSHEET® perfusion system

    PubMed Central

    2012-01-01

    Functional tissues generated under in vitro conditions are urgently needed in biomedical research. However, the engineering of tissues is rather difficult, since their development is influenced by numerous parameters. In consequence, a versatile culture system was developed to respond the unmet needs. Optimal adhesion for cells in this system is reached by the selection of individual biomaterials. To protect cells during handling and culture, the biomaterial is mounted onto a MINUSHEET® tissue carrier. While adherence of cells takes place in the static environment of a 24 well culture plate, generation of tissues is accomplished in one of several available perfusion culture containers. In the basic version a continuous flow of always fresh culture medium is provided to the developing tissue. In a gradient perfusion culture container epithelia are exposed to different fluids at the luminal and basal sides. Another special container with a transparent lid and base enables microscopic visualization of ongoing tissue development. A further container exhibits a flexible silicone lid to apply force onto the developing tissue thereby mimicking mechanical load that is required for developing connective and muscular tissue. Finally, stem/progenitor cells are kept at the interface of an artificial polyester interstitium within a perfusion culture container offering for example an optimal environment for the spatial development of renal tubules. The system presented here was evaluated by various research groups. As a result a variety of publications including most interesting applications were published. In the present paper these data were reviewed and analyzed. All of the results point out that the cell biological profile of engineered tissues can be strongly improved, when the introduced perfusion culture technique is applied in combination with specific biomaterials supporting primary adhesion of cells. PMID:23369669

  3. Parasites and steroid hormones: corticosteroid and sex steroid synthesis, their role in the parasite physiology and development.

    PubMed

    Romano, Marta C; Jiménez, Pedro; Miranda-Brito, Carolina; Valdez, Ricardo A

    2015-01-01

    In many cases parasites display highly complex life cycles that include the penetration and permanence of the larva or adults within host organs, but even in those that only have one host, reciprocal, intricate interactions occur. Evidence indicates that steroid hormones have an influence on the development and course of parasitic infections. The host gender's susceptibility to infection, and the related differences in the immune response are good examples of the host-parasite interplay. However, the capacity of these organisms to synthesize their own steroidogenic hormones still has more questions than answers. It is now well-known that many parasites synthesize ecdysteroids, but limited information is available on sex steroid and corticosteroid synthesis. This review intends to summarize some of the existing information in the field. In most, but not all parasitosis the host's hormonal environment determines the susceptibility, the course, and severity of parasite infections. In most cases the infection disturbs the host environment, and activates immune responses that end up affecting the endocrine system. Furthermore, sex steroids and corticosteroids may also directly modify the parasite reproduction and molting. Available information indicates that parasites synthesize some steroid hormones, such as ecdysteroids and sex steroids, and the presence and activity of related enzymes have been demonstrated. More recently, the synthesis of corticosteroid-like compounds has been shown in Taenia solium cysticerci and tapeworms, and in Taenia crassiceps WFU cysticerci. In-depth knowledge of the parasite's endocrine properties will contribute to understand their reproduction and reciprocal interactions with the host, and may also help designing tools to combat the infection in some clinical situations.

  4. Parasites and steroid hormones: corticosteroid and sex steroid synthesis, their role in the parasite physiology and development

    PubMed Central

    Romano, Marta C.; Jiménez, Pedro; Miranda-Brito, Carolina; Valdez, Ricardo A.

    2015-01-01

    In many cases parasites display highly complex life cycles that include the penetration and permanence of the larva or adults within host organs, but even in those that only have one host, reciprocal, intricate interactions occur. Evidence indicates that steroid hormones have an influence on the development and course of parasitic infections. The host gender's susceptibility to infection, and the related differences in the immune response are good examples of the host-parasite interplay. However, the capacity of these organisms to synthesize their own steroidogenic hormones still has more questions than answers. It is now well-known that many parasites synthesize ecdysteroids, but limited information is available on sex steroid and corticosteroid synthesis. This review intends to summarize some of the existing information in the field. In most, but not all parasitosis the host's hormonal environment determines the susceptibility, the course, and severity of parasite infections. In most cases the infection disturbs the host environment, and activates immune responses that end up affecting the endocrine system. Furthermore, sex steroids and corticosteroids may also directly modify the parasite reproduction and molting. Available information indicates that parasites synthesize some steroid hormones, such as ecdysteroids and sex steroids, and the presence and activity of related enzymes have been demonstrated. More recently, the synthesis of corticosteroid-like compounds has been shown in Taenia solium cysticerci and tapeworms, and in Taenia crassiceps WFU cysticerci. In-depth knowledge of the parasite's endocrine properties will contribute to understand their reproduction and reciprocal interactions with the host, and may also help designing tools to combat the infection in some clinical situations. PMID:26175665

  5. Drug treatment of tropical parasitic infections: recent achievements and developments.

    PubMed

    Stephenson, I; Wiselka, M

    2000-11-01

    Drug development offers potential solutions to a number of tropical health diseases, although the expense of pharmaceutical research and lack of return on investment has limited the production of new agents. The greatest successes have been through the development of single dose therapy and mass treatment control programmes for a number of diseases. We review some of the current treatment regimens for malaria, intestinal helminth infection, onchocerciasis, filariasis and schistosomiasis, and their use in clinical practice. Geographical spread and emergence of drug resistant parasites have hindered the control of malaria, the most important global parasitic infection. Artemisinin compounds have proved effective antimalarial agents producing rapid reduction of parasite load and can be used in combination treatment regimens to combat multidrug resistance. Intestinal helminth infections are widespread, giving rise to nutritional deficiencies and impaired childhood cognitive development. Pregnant women in developing countries are at increased risk of morbidity. Treatment with a single dose benzimidazole such as albendazole or mebendazole has beneficial effects on morbidity and rates of transmission. Diethylcarbamazine has been used in the treatment of onchocerciasis and human filariasis. A complicated escalating dose regimen over several weeks is associated with systemic and allergic reactions and may require corticosteroid cover. Simplified regimens for mass population treatment with ivermectin have proved useful and been used in combination with single dose albendazole and diethylcarbamazine. The African Programme for Onchocerciasis Control in West and Central Africa has been one of the most successful mass control programmes virtually eliminating new infections by a combination of chemotherapy, education and vector control. Schistosomiasis is of increasing importance as a result of the creation of new snail habitats by agricultural and economic development

  6. Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

    PubMed

    Roman, Marius A; Nair, Sukumaran; Tsui, Steven; Dunning, John; Parmar, Jasvir S

    2013-09-01

    There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

  7. Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

    PubMed Central

    Qvit, Nir; Schechtman, Deborah; Pena, Darlene Aparecida; Berti, Denise Aparecida; Soares, Chrislaine Oliveira; Miao, Qianqian; Liang, Liying (Annie); Baron, Lauren A.; Teh-Poot, Christian; Martínez-Vega, Pedro; Ramirez-Sierra, Maria Jesus; Churchill, Eric; Cunningham, Anna D.; Malkovskiy, Andrey V.; Federspiel, Nancy A.; Gozzo, Fabio Cesar; Torrecilhas, Ana Claudia; Manso Alves, Maria Julia; Jardim, Armando; Momar, Ndao; Dumonteil, Eric; Mochly-Rosen, Daria

    2016-01-01

    Parasitic diseases cause ∼500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosomareceptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. PMID:27054066

  8. [Health education for major parasitic diseases in rural community of China: current status and future development].

    PubMed

    Zhang, Jing; Lin, Dan-dan

    2013-08-01

    Owing to human parasitic diseases being related to behavior, the health education as an important measure to prevent parasite infections through human behavior intervention, has played an important role in the process of parasitic disease prevention and control in rural area of China. This paper comments on the development history of the health education for parasitic disease prevention and control, current intervention modes and the effect of the health education for parasitic diseases in rural area. This paper also summarizes the role and impact of different modes of the health education for parasitic disease prevention and control and gives some suggestions to future development of the health education in rural area under current prevalent situation of parasitic diseases.

  9. Postembryonic development of the parasitic amphipod Hyperia galba

    NASA Astrophysics Data System (ADS)

    Dittrich, Birgit

    1987-06-01

    Hyperia galba Montagu is associated with gelatinous zooplankton as are many species of the Hyperiidea. The hosts preferred in the European seas are the large scyphomedusae Aurelia aurita, Chrysaora hysoscella, Rhizostoma pulmo, Cyanea capillata and Cyanea lamarckii, which harbour the first developmental stages. The anamorphic development produces young that are incapable of swimming at the time of hatching. They are characterized by an embryonic abdomen without extremities and external segmentation; the eyes are not completely developed and the mouth is primitive lacking bristles, molar and incisor. The postembryonic development, described in detail, is subdivided into two phases: the pantochelis phase and the protopleon phase; the former comprises only one stage; the latter can be subdivided into four stages. In the course of postnatal development the larval organs are reduced and characters typical of the adult are gradually differentiated. H. galba plays an important role as obligatory endoparasite of scyphomedusae at least during the first stages of development; without a host this amphipod cannot survive, neither benthically nor in the plankton. The transition from life in the female's marsupium to endoparasitism in the jellyfish generally occurs during stage of the postembryonic development which is the first stage of the protopleon phase. The specific adaptations of its reproductive biology to a parasitic mode of life such as moult inhibition under starvation, development of larval organs and the behavioural patterns of the females as well as the young are described. Further, the influence of external factors such as temperature and food supply on the course of development is examined.

  10. Impact of next-generation technologies on exploring socioeconomically important parasites and developing new interventions.

    PubMed

    Cantacessi, Cinzia; Hofmann, Andreas; Campbell, Bronwyn E; Gasser, Robin B

    2015-01-01

    High-throughput molecular and computer technologies have become instrumental for systems biological explorations of pathogens, including parasites. For instance, investigations of the transcriptomes of different developmental stages of parasitic nematodes give insights into gene expression, regulation and function in a parasite, which is a significant step to understanding their biology, as well as interactions with their host(s) and disease. This chapter (1) gives a background on some key parasitic nematodes of socioeconomic importance, (2) describes sequencing and bioinformatic technologies for large-scale studies of the transcriptomes and genomes of these parasites, (3) provides some recent examples of applications and (4) emphasizes the prospects of fundamental biological explorations of parasites using these technologies for the development of new interventions to combat parasitic diseases.

  11. Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence.

    PubMed

    McNeilly, Tom N; Nisbet, Alasdair J

    2014-01-01

    Parasitic helminths reside in immunologically-exposed extracellular locations within their hosts, yet they are capable of surviving for extended periods. To enable this survival, these parasites have developed complex and multifaceted mechanisms to subvert or suppress host immunity. This review summarises current knowledge of immune modulation by helminth parasites of ruminants and the parasite-derived molecules involved in driving this modulation. Such immunomodulatory molecules have considerable promise as vaccine targets, as neutralisation of their function is predicted to enhance anti-parasite immunity and, as such, current knowledge in this area is presented herein. Furthermore, we summarise current evidence that, as well as affecting parasite-specific immunity, immune modulation by these parasites may also affect the ability of ruminant hosts to control concurrent diseases or mount effective responses to vaccination.

  12. Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence

    PubMed Central

    McNeilly, Tom N.; Nisbet, Alasdair J.

    2014-01-01

    Parasitic helminths reside in immunologically-exposed extracellular locations within their hosts, yet they are capable of surviving for extended periods. To enable this survival, these parasites have developed complex and multifaceted mechanisms to subvert or suppress host immunity. This review summarises current knowledge of immune modulation by helminth parasites of ruminants and the parasite-derived molecules involved in driving this modulation. Such immunomodulatory molecules have considerable promise as vaccine targets, as neutralisation of their function is predicted to enhance anti-parasite immunity and, as such, current knowledge in this area is presented herein. Furthermore, we summarise current evidence that, as well as affecting parasite-specific immunity, immune modulation by these parasites may also affect the ability of ruminant hosts to control concurrent diseases or mount effective responses to vaccination. PMID:25292481

  13. Larval amphibian growth and development under varying density: are parasitized individuals poor competitors?

    PubMed

    Koprivnikar, J; Forbes, M R; Baker, R L

    2008-03-01

    Population density and infection with parasites often are important factors affecting the growth and development of individuals. How these factors co-occur and interact in nature should have important consequences for individual fitness and higher-order phenomena, such as population dynamics of hosts and their interactions with other species. However, few studies have examined the joint effects of density and parasitism on host growth and development. We examined the co-influences of rearing density and parasitism, by the trematode Echinostoma trivolvis, on the growth and development of larval frogs, Rana (=Lithobates) pipiens. We also examined the potential role of parasite-mediated intraspecific competition by observing how unparasitized individuals performed when housed with other unparasitized tadpoles, versus housing with a combination of unparasitized and parasitized hosts. Mean mass and mean developmental stage were reduced under high rearing densities. The presence of parasitized conspecifics had no significant effect, but there was a significant interaction of density and parasitism presence on host mass, due to the fact that parasitized conspecifics grew poorly at high densities. Unparasitized individuals reared with parasitized and unparasitized conspecifics fared no better than unparasitized individuals reared only with one another. This result indicates that infected hosts compete as much as uninfected hosts for resources, even though infected individuals have reduced mass under high-density conditions. Resource acquisition and resource allocation are different processes, and parasitism, if it only affects the latter, might not have a discernible impact on competitive interactions.

  14. Lactate retards the development of erythrocytic stages of the human malaria parasite Plasmodium falciparum.

    PubMed

    Hikosaka, Kenji; Hirai, Makoto; Komatsuya, Keisuke; Ono, Yasuo; Kita, Kiyoshi

    2015-06-01

    The intraerythrocytic form of the human malaria parasite Plasmodium falciparum relies on glycolysis for its energy requirements. In glycolysis, lactate is an end product. It is therefore known that lactate accumulates in in vitro culture; however, its influence on parasite growth remains unknown. Here we investigated the effect of lactate on the development of P. falciparum during in vitro culture under lactate supplementation in detail. Results revealed that lactate retarded parasite development and reduced the number of merozoites in the schizont stage. These findings suggest that lactate has the potential to affect parasite development.

  15. Egg puncture allows shiny cowbirds to assess host egg development and suitability for parasitism

    PubMed Central

    Massoni, V.; Reboreda, J. C.

    1999-01-01

    Parasitic cowbirds and cuckoos generally reduce the clutch size of the hosts they parasitize by removing or destroying some of their eggs. Shiny cowbirds (Molothrus bonariensis) puncture their hosts' eggs both when parasitizing the nests and also when they do not parasitize them. We propose that, by puncturing the host's eggs, shiny cowbirds gain an informational benefit. They assess the degree of development of the host's embryos and so avoid laying in nests that would not provide enough incubation time for the parasitic eggs to hatch. Two predictions follow: (i) punctures should occur in advance or immediately before parasitic events, and (ii) the occurrence of parasitism should depend on the degree of development of the host's embryos when punctures occurred, i.e. on the stage of incubation. Both predictions are supported by our data of shiny cowbirds parasitizing yellow-winged blackbirds (Agelaius thilius). Egg punctures are not used to reset the host's nesting attempt when shiny cowbirds do not parasitize the nests. We discuss the potential mechanisms implicated in egg development assessment and propose a critical experiment to test this hypothesis.

  16. Lipopeptide Nanoparticles: Development of Vaccines against Hookworm Parasite.

    PubMed

    Fuaad, Abdullah A H Ahmad; Pearson, Mark S; Pickering, Darren A; Becker, Luke; Zhao, Guangzu; Loukas, Alex C; Skwarczynski, Mariusz; Toth, Istvan

    2015-10-01

    Necator americanus (hookworm) infects over half a billion people worldwide. Anthelminthic drugs are commonly used to treat the infection; however, vaccination is a more favorable strategy to combat this parasite. We designed new B-cell peptide epitopes based on the aspartic protease of N. americanus (Na-APR-1). The peptides were conjugated to self-adjuvanting lipid core peptide (LCP) systems via stepwise solid-phase peptide synthesis (SPPS) and copper catalyst azide-alkyne cycloaddition (CuAAC) reactions. The LCP vaccine candidates were able to self-assemble into nanoparticles, were administered to mice without the use of additional adjuvant, and generated antibodies that recognized the parent epitope. However, only one LCP derivative was able to produce a high titer of antibodies specific to Na-APR-1; circular dichroism analyses of this compound showed a β-sheet conformation for the incorporated epitope. This study provides important insight in epitope and delivery system design for the development of a vaccine against hookworm infections.

  17. The Development of a Thin-Filmed, Non-Invasive Tissue Perfusion Sensor to Quantify Capillary Pressure Occlusion of Explanted Organs.

    PubMed

    OBrien, Timothy J; Roghani, Ali R; Jones, Philip A; Aardema, Charles H; Robertson, John L; Diller, Thomas E

    2016-10-05

    A new thin-filmed perfusion sensor was developed using a heat flux gauge, thin-film thermocouple, and a heating element. This sensor, termed "CHFT+", is an enhancement of the previously established CHFT (combined heat flux - temperature) sensor technology predominately used to quantify the severity of burns [1]. The CHFT+ sensor was uniquely designed to measure tissue perfusion on explanted organs destined for transplantation, but could be functionalized and used in a wide variety of other biomedical applications. Exploiting the thin and semi-flexible nature of the new CHFT+ sensor assembly, perfusion measurements can be made from the underside of the organ - providing a quantitative, indirect measure of capillary pressure occlusion. Results from a live tissue test demonstrated, for the first time, the effects of pressure occlusion on an explanted porcine kidney. CHFT+ sensors were placed on top of and underneath 18 kidneys to measure and compare perfusion at perfusate temperatures of 5˚C and 20˚C. The data collected shows greater perfusion on the topside than the underside of the specimen for the length of the experiment. This indicates that pressure occlusion is truly affecting the perfusion and thus, the overall preservation of explanted organs. Moreover, the results demonstrate the effect of preservation temperature on the tissue vasculature. Focusing on the topside perfusion only, the 20˚C perfusion was greater than the 5˚C perfusion, likely due to the vasoconstrictive response at the lower perfusion temperatures.

  18. Recent developments in drug discovery against the protozoal parasites Cryptosporidium and Toxoplasma.

    PubMed

    Chellan, Prinessa; Sadler, Peter J; Land, Kirkwood M

    2017-04-01

    Apicomplexan parasites cause some of the most devastating human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. New drug discovery is imperative in light of increased resistance. In this digest article, we briefly explore some of the recent and promising developments in new drug discovery against two apicomplexan parasites, Cryptosporidium and Toxoplasma.

  19. A broad analysis of resistance development in the malaria parasite.

    PubMed

    Corey, Victoria C; Lukens, Amanda K; Istvan, Eva S; Lee, Marcus C S; Franco, Virginia; Magistrado, Pamela; Coburn-Flynn, Olivia; Sakata-Kato, Tomoyo; Fuchs, Olivia; Gnädig, Nina F; Goldgof, Greg; Linares, Maria; Gomez-Lorenzo, Maria G; De Cózar, Cristina; Lafuente-Monasterio, Maria Jose; Prats, Sara; Meister, Stephan; Tanaseichuk, Olga; Wree, Melanie; Zhou, Yingyao; Willis, Paul A; Gamo, Francisco-Javier; Goldberg, Daniel E; Fidock, David A; Wirth, Dyann F; Winzeler, Elizabeth A

    2016-06-15

    Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a diverse set of antimalarial compounds to investigate the acquisition of drug resistance and the degree of cross-resistance against common resistance alleles. We assess cross-resistance using a set of 15 parasite lines carrying resistance-conferring alleles in pfatp4, cytochrome bc1, pfcarl, pfdhod, pfcrt, pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase or hsp90. Subsequently, we assess whether resistant parasites can be obtained after several rounds of drug selection. Twenty-three of the 48 in vitro selections result in resistant parasites, with time to resistance onset ranging from 15 to 300 days. Our data indicate that pre-existing resistance may not be a major hurdle for novel-target antimalarial candidates, and focusing our attention on fast-killing compounds may result in a slower onset of clinical resistance.

  20. A broad analysis of resistance development in the malaria parasite

    PubMed Central

    Corey, Victoria C.; Lukens, Amanda K.; Istvan, Eva S.; Lee, Marcus C. S.; Franco, Virginia; Magistrado, Pamela; Coburn-Flynn, Olivia; Sakata-Kato, Tomoyo; Fuchs, Olivia; Gnädig, Nina F.; Goldgof, Greg; Linares, Maria; Gomez-Lorenzo, Maria G.; De Cózar, Cristina; Lafuente-Monasterio, Maria Jose; Prats, Sara; Meister, Stephan; Tanaseichuk, Olga; Wree, Melanie; Zhou, Yingyao; Willis, Paul A.; Gamo, Francisco-Javier; Goldberg, Daniel E.; Fidock, David A.; Wirth, Dyann F.; Winzeler, Elizabeth A.

    2016-01-01

    Microbial resistance to chemotherapy has caused countless deaths where malaria is endemic. Chemotherapy may fail either due to pre-existing resistance or evolution of drug-resistant parasites. Here we use a diverse set of antimalarial compounds to investigate the acquisition of drug resistance and the degree of cross-resistance against common resistance alleles. We assess cross-resistance using a set of 15 parasite lines carrying resistance-conferring alleles in pfatp4, cytochrome bc1, pfcarl, pfdhod, pfcrt, pfmdr, pfdhfr, cytoplasmic prolyl t-RNA synthetase or hsp90. Subsequently, we assess whether resistant parasites can be obtained after several rounds of drug selection. Twenty-three of the 48 in vitro selections result in resistant parasites, with time to resistance onset ranging from 15 to 300 days. Our data indicate that pre-existing resistance may not be a major hurdle for novel-target antimalarial candidates, and focusing our attention on fast-killing compounds may result in a slower onset of clinical resistance. PMID:27301419

  1. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    SciTech Connect

    Adam, Jean-Francois

    2005-04-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size <50x50 {mu}m{sup 2}) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal

  2. The isolated perfused rat kidney model: a useful tool for drug discovery and development.

    PubMed

    Taft, David R

    2004-01-01

    Over the past three decades, the Isolated Perfused Rat Kidney (IPK) has been used to study numerous aspects of renal drug disposition. Among the available ex-vivo methods to study renal transport, the IPK allows for elucidation of the overall contributions of renal transport mechanisms on drug excretion. Therefore, IPK studies can provide a bridge between in vitro findings and in vivo disposition. This review paper begins with a detailed overview of IPK methodology (system components, surgical procedure, study design). Various applications of the IPK are then presented. These applications include characterizing renal excretion mechanisms, screening for clinically significant drug interactions, studying renal drug metabolism, and correlating renal drug disposition with drug-induced changes in kidney function. Lastly, the role of IPK studies in drug development is discussed. Demonstrated correlations between IPK data and clinical outcomes make the IPK model a potentially useful tool for drug discovery and evaluation.

  3. A Newly Developed Perfused Umbrella Electrode for Radiofrequency Ablation: An Ex Vivo Evaluation Study in Bovine Liver

    SciTech Connect

    Bruners, Philipp Pfeffer, Jochen; Kazim, Rana M.; Guenther, Rolf W.; Schmitz-Rode, Thomas; Mahnken, Andreas H.

    2007-09-15

    The purpose of this study was to evaluate the effectiveness of a newly developed perfused monopolar radiofrequency (RF) probe with an umbrella-shaped array. A perfused umbrella-shaped monopolar RF probe based on a LeVeen electrode (Boston Scientific Corp., Natick, MA, USA) with a 3-cm array diameter was developed. Five different configurations of this electrode were tested: (a) perfusion channel/endhole, (b) perfusion channel/endhole + sideholes, (c) 1 cm insulation removed at the tip, (d) 1 cm insulation removed at the tip + perfusion channel/endhole, and (e) 1 cm insulation removed at the tip + perfusion channel/endhole + sideholes. An unmodified LeVeen electrode served as a reference standard. RF ablations were performed in freshly excised bovine liver using a commercial monopolar RF system with a 200-W generator (RF 3000; Boston Scientific Corp.). Each electrode was tested 10 times applying the vendor's recommended ablation protocol combined with the preinjection of 2 ml 0.9% saline. Volumes and shapes of the lesions were compared. Lesions generated with the original LeVeen electrode showed a mean volume of 12.74 {+-} 0.52 cm{sup 3}. Removing parts of the insulation led to larger coagulation volumes (22.65 {+-} 2.12 cm{sup 3}). Depending on the configuration, saline preinjection resulted in a further increase in coagulation volume (25.22 {+-} 3.37 to 31.28 {+-} 2.32 cm{sup 3}). Besides lesion volume, the shape of the ablation zone was influenced by the configuration of the electrode used. We conclude that saline preinjection in combination with increasing the active tip length of the umbrella-shaped LeVeen RF probe allows the reliable ablation of larger volumes in comparison to the originally configured electrode.

  4. The development of a bioreactor to perfuse radially-confined hydrogel constructs: design and characterization of mass transport properties.

    PubMed

    Eniwumide, Joshua O; Lee, David A; Bader, Dan L

    2009-01-01

    Limitations to nutrient transport provide a challenge to the development of 3D tissue-engineered constructs. A heterogeneous distribution of viable cells and functional matrix within the developing tissue is a common consequence. In the present study, a bioreactor was developed to perfuse fluid through cylindrical agarose constructs. The transport and distribution of dextran molecules (FD-4, FD-500, FD-2000) within the agarose was visualized in order to determine the bioreactors effectiveness for transport enhancement. By 24 h, the perfusion bioreactor achieved 529%, 395% and 294% higher concentrations of FD-4, FD-500 and FD-2000, respectively, than those solely due to diffusion. Of particular interest was the effectiveness of the bioreactor to transport molecules to the central region of the constructs. In this respect, the perfusion bioreactor was found to increase transportation of FD-4, FD-500 and FD-2000 by 30%, 291% and 222% over that of diffusion. Articular chondrocytes were cultured and perfused using the bioreactor. The improved molecular transport achieved led to an average 75% and 1340% increase of DNA and sulphated GAG, respectively at 20 days. More significantly was the 106% and 1603% increase of DNA and GAG, respectively, achieved at the central core of the 3D constructs.

  5. A class of tricyclic compounds blocking malaria parasite oocyst development and transmission.

    PubMed

    Eastman, Richard T; Pattaradilokrat, Sittiporn; Raj, Dipak K; Dixit, Saurabh; Deng, Bingbing; Miura, Kazutoyo; Yuan, Jing; Tanaka, Takeshi Q; Johnson, Ronald L; Jiang, Hongying; Huang, Ruili; Williamson, Kim C; Lambert, Lynn E; Long, Carole; Austin, Christopher P; Wu, Yimin; Su, Xin-Zhuan

    2013-01-01

    Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a Plasmodium falciparum ABC transporter (Pf14_0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of P. falciparum and the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of Plasmodium cynomolgi infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication.

  6. Development and Assessment of Transgenic Rodent Parasites for the Preclinical Evaluation of Malaria Vaccines.

    PubMed

    Espinosa, Diego A; Radtke, Andrea J; Zavala, Fidel

    2016-01-01

    Rodent transgenic parasites are useful tools for the preclinical evaluation of malaria vaccines. Over the last decade, several studies have reported the development of transgenic rodent parasites expressing P. falciparum antigens for the assessment of vaccine-induced immune responses, which traditionally have been limited to in vitro assays. However, the genetic manipulation of rodent Plasmodium species can have detrimental effects on the parasite's infectivity and development. In this chapter, we present a few guidelines for designing transfection plasmids, which should improve transfection efficiency and facilitate the generation of functional transgenic parasite strains. In addition, we provide a transfection protocol for the development of transgenic P. berghei parasites as well as practical methods to assess the viability and infectivity of these newly generated strains throughout different stages of their life cycle. These techniques should allow researchers to develop novel rodent malaria parasites expressing antigens from human malaria species and to determine whether these transgenic strains are fully infectious and thus represent stringent platforms for the in vivo evaluation of malaria vaccine candidates.

  7. Computational fluid dynamics modelling of perfusion measurements in dynamic contrast-enhanced computed tomography: development, validation and clinical applications

    NASA Astrophysics Data System (ADS)

    Peladeau-Pigeon, M.; Coolens, C.

    2013-09-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is an imaging tool that aids in evaluating functional characteristics of tissue at different stages of disease management: diagnostic, radiation treatment planning, treatment effectiveness, and monitoring. Clinical validation of DCE-derived perfusion parameters remains an outstanding problem to address prior to perfusion imaging becoming a widespread standard as a non-invasive quantitative measurement tool. One approach to this validation process has been the development of quality assurance phantoms in order to facilitate controlled perfusion ex vivo. However, most of these systems fail to establish and accurately replicate physiologically relevant capillary permeability and exchange performance. The current work presents the first step in the development of a prospective suite of physics-based perfusion simulations based on coupled fluid flow and particle transport phenomena with the goal of enhancing the understanding of clinical contrast agent kinetics. Existing knowledge about a controllable, two-compartmental fluid exchange phantom was used to validate the computational fluid dynamics (CFD) simulation model presented herein. The sensitivity of CFD-derived contrast uptake curves to contrast injection parameters, including injection duration and flow rate, were quantified and found to be within 10% accuracy. The CFD model was employed to evaluate two commonly used clinical kinetic algorithms used to derive perfusion parameters: Fick's principle and the modified Tofts model. Neither kinetic model was able to capture the true transport phenomena it aimed to represent but if the overall contrast concentration after injection remained identical, then successive DCE-CT evaluations could be compared and could indeed reflect differences in regional tissue flow. This study sets the groundwork for future explorations in phantom development and pharmaco-kinetic modelling, as well as the development of novel contrast

  8. Development of a realistic, dynamic digital brain phantom for CT perfusion validation

    NASA Astrophysics Data System (ADS)

    Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

    2016-03-01

    Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

  9. Development of Coronary Vasospasm during Adenosine-Stress Myocardial Perfusion CT Imaging.

    PubMed

    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Seo; Kwon, Woon Jeong

    2015-01-01

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  10. A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development.

    PubMed

    Malleret, Benoît; Claser, Carla; Ong, Alice Soh Meoy; Suwanarusk, Rossarin; Sriprawat, Kanlaya; Howland, Shanshan Wu; Russell, Bruce; Nosten, Francois; Rénia, Laurent

    2011-01-01

    Microscopic examination of Giemsa-stained thin blood smears remains the gold standard method used to quantify and stage malaria parasites. However, this technique is tedious, and requires trained microscopists. We have developed a fast and simple flow cytometry method to quantify and stage, various malaria parasites in red blood cells in whole blood or in vitro cultured Plasmodium falciparum. The parasites were stained with dihydroethidium and Hoechst 33342 or SYBR Green I and leukocytes were identified with an antibody against CD45. Depending on the DNA stains used, samples were analyzed using different models of flow cytometers. This protocol, which does not require any washing steps, allows infected red blood cells to be distinguished from leukocytes, as well as allowing non-infected reticulocytes and normocytes to be identified. It also allows assessing the proportion of parasites at different developmental stages. Lastly, we demonstrate how this technique can be applied to antimalarial drug testing.

  11. Limonene Arrests Parasite Development and Inhibits Isoprenylation of Proteins in Plasmodium falciparum

    PubMed Central

    Moura, Ivan Cruz; Wunderlich, Gerhard; Uhrig, Maria L.; Couto, Alicia S.; Peres, Valnice J.; Katzin, Alejandro M.; Kimura, Emília A.

    2001-01-01

    Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that in Plasmodium falciparum, a number of proteins were labeled upon incubation of intraerythrocytic forms with either [3H]farnesyl pyrophosphate or [3H]geranylgeranyl pyrophosphate. By thin-layer chromatography, we showed that attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism in this parasite. Incubation of blood-stage P. falciparum treated with the isoprenylation inhibitor limonene significantly decreased the parasites' progression from the ring stage to the trophozoite stage and at 1.22 mM, 50% of the parasites died after the first cycle. Using Ras- and Rap-specific monoclonal antibodies, putative Rap and Ras proteins of P. falciparum were immunoprecipitated. Upon treatment with 0.5 mM limonene, isoprenylation of these proteins was significantly decreased, possibly explaining the observed arrest of parasite development. PMID:11502528

  12. MHC, parasites and antler development in red deer: no support for the Hamilton & Zuk hypothesis.

    PubMed

    Buczek, M; Okarma, H; Demiaszkiewicz, A W; Radwan, J

    2016-03-01

    The Hamilton-Zuk hypothesis proposes that the genetic benefits of preferences for elaborated secondary sexual traits have their origins in the arms race between hosts and parasites, which maintains genetic variance in parasite resistance. Infection, in turn, can be reflected in the expression of costly sexual ornaments. However, the link between immune genes, infection and the expression of secondary sexual traits has rarely been investigated. Here, we explored whether the presence and identity of functional variants (supertypes) of the highly polymorphic major histocompatibility complex (MHC), which is responsible for the recognition of parasites, predict the load of lung and gut parasites and antler development in the red deer (Cervus elaphus). While we found MHC supertypes to be associated with infection by a number of parasite species, including debilitating lung nematodes, we did not find support for the Hamilton-Zuk hypothesis. On the contrary, we found that lung nematode load was positively associated with antler development. We also found that the supertypes that were associated with resistance to certain parasites at the same time cause susceptibility to others. Such trade-offs may undermine the potential genetic benefits of mate choice for resistant partners.

  13. Parasitic Colitis

    PubMed Central

    Hechenbleikner, Elizabeth M.; McQuade, Jennifer A.

    2015-01-01

    Over one billion people worldwide harbor intestinal parasites. Parasitic intestinal infections have a predilection for developing countries due to overcrowding and poor sanitation but are also found in developed nations, such as the United States, particularly in immigrants or in the setting of sporadic outbreaks. Although the majority of people are asymptomatically colonized with parasites, the clinical presentation can range from mild abdominal discomfort or diarrhea to serious complications, such as perforation or bleeding. Protozoa and helminths (worms) are the two major classes of intestinal parasites. Protozoal intestinal infections include cryptosporidiosis, cystoisosporiasis, cyclosporiasis, balantidiasis, giardiasis, amebiasis, and Chagas disease, while helminth infections include ascariasis, trichuriasis, strongyloidiasis, enterobiasis, and schistosomiasis. Intestinal parasites are predominantly small intestine pathogens but the large intestine is also frequently involved. This article highlights important aspects of parasitic infections of the colon including epidemiology, transmission, symptoms, and diagnostic methods as well as appropriate medical and surgical treatment. PMID:26034403

  14. Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa.

    PubMed

    Mendes, Antonio M; Schlegelmilch, Timm; Cohuet, Anna; Awono-Ambene, Parfait; De Iorio, Maria; Fontenille, Didier; Morlais, Isabelle; Christophides, George K; Kafatos, Fotis C; Vlachou, Dina

    2008-05-16

    In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists.

  15. Dynamics of sterol synthesis during development of Leishmania spp. parasites to their virulent form.

    PubMed

    Yao, Chaoqun; Wilson, Mary E

    2016-04-12

    The Leishmania spp. protozoa, the causative agents of the "neglected" tropical disease leishmaniasis, are transmitted to mammals by sand fly vectors. Within the sand fly, parasites transform from amastigotes to procyclic promastigotes, followed by development of virulent (metacyclic) promastigote forms. The latter are infectious to mammalian hosts. Biochemical components localized in the parasite plasma membrane such as proteins and sterols play a pivotal role in Leishmania pathogenesis. Leishmania spp. lack the enzymes for cholesterol synthesis, and the dynamics of sterol acquisition and biosynthesis in parasite developmental stages are not understood. We hypothesized that dynamic changes in sterol composition during metacyclogenesis contribute to the virulence of metacyclic promastigotes. Sterols were extracted from logarithmic phase or metacyclic promastigotes grown in liquid culture with or without cholesterol, and analyzed qualitatively and quantitatively by gas chromatograph-mass spectrometry (GC-MS). TriTrypDB was searched for identification of genes involved in Leishmania sterol biosynthetic pathways. In total nine sterols were identified. There were dynamic changes in sterols during promastigote metacyclogenesis. Cholesterol in the culture medium affected sterol composition in different parasite stages. There were qualitative and relative quantitative differences between the sterol content of virulent versus avirulent parasite strains. A tentative sterol biosynthetic pathway in Leishmania spp. promastigotes was identified. Significant differences in sterol composition were observed between promastigote stages, and between parasites exposed to different extracellular cholesterol in the environment. These data lay the foundation for further investigating the role of sterols in the pathogenesis of Leishmania spp. infections.

  16. Development and Characterization of a Parallelizable Perfusion Bioreactor for 3D Cell Culture

    PubMed Central

    Egger, Dominik; Fischer, Monica; Clementi, Andreas; Ribitsch, Volker; Hansmann, Jan; Kasper, Cornelia

    2017-01-01

    The three dimensional (3D) cultivation of stem cells in dynamic bioreactor systems is essential in the context of regenerative medicine. Still, there is a lack of bioreactor systems that allow the cultivation of multiple independent samples under different conditions while ensuring comprehensive control over the mechanical environment. Therefore, we developed a miniaturized, parallelizable perfusion bioreactor system with two different bioreactor chambers. Pressure sensors were also implemented to determine the permeability of biomaterials which allows us to approximate the shear stress conditions. To characterize the flow velocity and shear stress profile of a porous scaffold in both bioreactor chambers, a computational fluid dynamics analysis was performed. Furthermore, the mixing behavior was characterized by acquisition of the residence time distributions. Finally, the effects of the different flow and shear stress profiles of the bioreactor chambers on osteogenic differentiation of human mesenchymal stem cells were evaluated in a proof of concept study. In conclusion, the data from computational fluid dynamics and shear stress calculations were found to be predictable for relative comparison of the bioreactor geometries, but not for final determination of the optimal flow rate. However, we suggest that the system is beneficial for parallel dynamic cultivation of multiple samples for 3D cell culture processes.

  17. Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models.

    PubMed

    Strüver, Kay; Friess, Wolfgang; Hedtrich, Sarah

    2017-01-01

    Reconstructed skin models are suitable test systems for toxicity testing and for basic investigations on (patho-)physiological aspects of human skin. Reconstructed human skin, however, has clear limitations such as the lack of immune cells and a significantly weaker skin barrier function compared to native human skin. Potential reasons for the latter might be the lack of mechanical forces during skin model cultivation which is performed classically in static well-plate setups. Mechanical forces and shear stress have a major impact on tissue formation and, hence, tissue engineering. In the present work, a perfusion platform was developed allowing dynamic cultivation of in vitro skin models. The platform was designed to cultivate reconstructed skin at the air-liquid interface with a laminar and continuous medium flow below the dermis equivalent. Histological investigations confirmed the formation of a significantly thicker stratum corneum compared to the control cultivated under static conditions. Moreover, the skin differentiation markers involucrin and filaggrin as well as the tight junction proteins claudin 1 and occludin showed increased expression in the dynamically cultured skin models. Unexpectedly, despite improved differentiation, the skin barrier function of the dynamically cultivated skin models was not enhanced compared with the skin models cultivated under static conditions. © 2017 S. Karger AG, Basel.

  18. Development of the orpheus perfusion simulator for use in high-fidelity extracorporeal membrane oxygenation simulation.

    PubMed

    Lansdowne, William; Machin, David; Grant, David J

    2012-12-01

    Despite its life-sustaining potential, extracorporeal membrane oxygenation (ECMO) remains a complex treatment modality for which close teamwork is imperative with a high risk of adverse events leading to significant morbidity and mortality. The provision of adequate training and continuing education is key in mitigating these risks. Traditional training for ECMO has relied predominantly on didactic education and hands-on water drills. These methods may overemphasize cognitive skills while underemphasizing technical skills and completely ignoring team and human factor skills. These water drills are often static, lacking the time pressure, typical alarms, and a sense of urgency inherent to actual critical ECMO scenarios. Simulation-based training provides an opportunity for staff to develop and maintain technical proficiency in high-risk, infrequent events without fear of harming patients. In addition, it provides opportunities for interdisciplinary training and improved communication and teamwork among team members (1). Although simulation has become widely accepted for training of practitioners from many disciplines, there are currently, to our knowledge, no commercially available dedicated high-fidelity ECMO simulators. Our article describes the modification of the Orpheus Perfusion Simulator and its incorporation into a fully immersive, high-fidelity, point-of-care ECMO simulation model.

  19. Development of humanized mouse models to study human malaria parasite infection.

    PubMed

    Vaughan, Ashley M; Kappe, Stefan H I; Ploss, Alexander; Mikolajczak, Sebastian A

    2012-05-01

    Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future.

  20. Irritable Bowel Syndrome and Gastrointestinal Parasite Infection in a Developing Nation Environment

    PubMed Central

    Morgan, Douglas R.; Benshoff, Matthew; Cáceres, Mercedes; Becker-Dreps, Sylvia; Cortes, Loreto; Martin, Christopher F.; Schmulson, Max; Peña, Rodolfo

    2012-01-01

    Postinfectious IBS is defined in the industrialized world as IBS onset following a sentinel gastrointestinal infection. In developing nations, where repeated bacterial and parasitic gastrointestinal infections are common, the IBS pathophysiology may be altered. Our aim was to investigate the relationship between intestinal parasite infection and IBS in the “nonsterile” developing world environment. IBS subjects were identified from a population-based sample of 1624 participants using the Rome II Modular Questionnaire. Stool samples from cases and randomly selected controls were examined for ova and parasites. Logistic regression models explored the relationship between IBS and parasite infection. The overall IBS prevalence among participants was 13.2% (9.3% males, 15.9% females). There was no difference in parasite carriage between IBS cases and controls, 16.6% versus 15.4% (P = 0.78), nor among IBS subtypes. The pathophysiology of post-infectious IBS may be altered in the developing world as compared to industrialized nations and warrants investigation. PMID:22474433

  1. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  2. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  3. Development and validation of a segmentation-free polyenergetic algorithm for dynamic perfusion computed tomography.

    PubMed

    Lin, Yuan; Samei, Ehsan

    2016-07-01

    Dynamic perfusion imaging can provide the morphologic details of the scanned organs as well as the dynamic information of blood perfusion. However, due to the polyenergetic property of the x-ray spectra, beam hardening effect results in undesirable artifacts and inaccurate CT values. To address this problem, this study proposes a segmentation-free polyenergetic dynamic perfusion imaging algorithm (pDP) to provide superior perfusion imaging. Dynamic perfusion usually is composed of two phases, i.e., a precontrast phase and a postcontrast phase. In the precontrast phase, the attenuation properties of diverse base materials (e.g., in a thorax perfusion exam, base materials can include lung, fat, breast, soft tissue, bone, and metal implants) can be incorporated to reconstruct artifact-free precontrast images. If patient motions are negligible or can be corrected by registration, the precontrast images can then be employed as a priori information to derive linearized iodine projections from the postcontrast images. With the linearized iodine projections, iodine perfusion maps can be reconstructed directly without the influence of various influential factors, such as iodine location, patient size, x-ray spectrum, and background tissue type. A series of simulations were conducted on a dynamic iodine calibration phantom and a dynamic anthropomorphic thorax phantom to validate the proposed algorithm. The simulations with the dynamic iodine calibration phantom showed that the proposed algorithm could effectively eliminate the beam hardening effect and enable quantitative iodine map reconstruction across various influential factors. The error range of the iodine concentration factors ([Formula: see text]) was reduced from [Formula: see text] for filtered back-projection (FBP) to [Formula: see text] for pDP. The quantitative results of the simulations with the dynamic anthropomorphic thorax phantom indicated that the maximum error of iodine concentrations can be reduced from

  4. Using process algebra to develop predator-prey models of within-host parasite dynamics.

    PubMed

    McCaig, Chris; Fenton, Andy; Graham, Andrea; Shankland, Carron; Norman, Rachel

    2013-07-21

    As a first approximation of immune-mediated within-host parasite dynamics we can consider the immune response as a predator, with the parasite as its prey. In the ecological literature of predator-prey interactions there are a number of different functional responses used to describe how a predator reproduces in response to consuming prey. Until recently most of the models of the immune system that have taken a predator-prey approach have used simple mass action dynamics to capture the interaction between the immune response and the parasite. More recently Fenton and Perkins (2010) employed three of the most commonly used prey-dependent functional response terms from the ecological literature. In this paper we make use of a technique from computing science, process algebra, to develop mathematical models. The novelty of the process algebra approach is to allow stochastic models of the population (parasite and immune cells) to be developed from rules of individual cell behaviour. By using this approach in which individual cellular behaviour is captured we have derived a ratio-dependent response similar to that seen in the previous models of immune-mediated parasite dynamics, confirming that, whilst this type of term is controversial in ecological predator-prey models, it is appropriate for models of the immune system.

  5. Development and Application of a Simple Plaque Assay for the Human Malaria Parasite Plasmodium falciparum

    PubMed Central

    Thomas, James A.; Collins, Christine R.; Das, Sujaan; Hackett, Fiona; Graindorge, Arnault; Bell, Donald; Deu, Edgar; Blackman, Michael J.

    2016-01-01

    Malaria is caused by an obligate intracellular protozoan parasite that replicates within and destroys erythrocytes. Asexual blood stages of the causative agent of the most virulent form of human malaria, Plasmodium falciparum, can be cultivated indefinitely in vitro in human erythrocytes, facilitating experimental analysis of parasite cell biology, biochemistry and genetics. However, efforts to improve understanding of the basic biology of this important pathogen and to develop urgently required new antimalarial drugs and vaccines, suffer from a paucity of basic research tools. This includes a simple means of quantifying the effects of drugs, antibodies and gene modifications on parasite fitness and replication rates. Here we describe the development and validation of an extremely simple, robust plaque assay that can be used to visualise parasite replication and resulting host erythrocyte destruction at the level of clonal parasite populations. We demonstrate applications of the plaque assay by using it for the phenotypic characterisation of two P. falciparum conditional mutants displaying reduced fitness in vitro. PMID:27332706

  6. Sexual development in Plasmodium parasites: knowing when it's time to commit.

    PubMed

    Josling, Gabrielle A; Llinás, Manuel

    2015-09-01

    Malaria is a devastating infectious disease that is caused by blood-borne apicomplexan parasites of the genus Plasmodium. These pathogens have a complex lifecycle, which includes development in the anopheline mosquito vector and in the liver and red blood cells of mammalian hosts, a process which takes days to weeks, depending on the Plasmodium species. Productive transmission between the mammalian host and the mosquito requires transitioning between asexual and sexual forms of the parasite. Blood- stage parasites replicate cyclically and are mostly asexual, although a small fraction of these convert into male and female sexual forms (gametocytes) in each reproductive cycle. Despite many years of investigation, the molecular processes that elicit sexual differentiation have remained largely unknown. In this Review, we highlight several important recent discoveries that have identified epigenetic factors and specific transcriptional regulators of gametocyte commitment and development, providing crucial insights into this obligate cellular differentiation process.

  7. A transcriptional switch underlies commitment to sexual development in malaria parasites.

    PubMed

    Kafsack, Björn F C; Rovira-Graells, Núria; Clark, Taane G; Bancells, Cristina; Crowley, Valerie M; Campino, Susana G; Williams, April E; Drought, Laura G; Kwiatkowski, Dominic P; Baker, David A; Cortés, Alfred; Llinás, Manuel

    2014-03-13

    The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal. Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci prone to spontaneous activation. Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.

  8. Developing an Apicomplexan DNA Barcoding System to Detect Blood Parasites of Small Coral Reef Fishes.

    PubMed

    Renoux, Lance P; Dolan, Maureen C; Cook, Courtney A; Smit, Nico J; Sikkel, Paul C

    2017-08-01

    Apicomplexan parasites are obligate parasites of many species of vertebrates. To date, there is very limited understanding of these parasites in the most-diverse group of vertebrates, actinopterygian fishes. While DNA barcoding targeting the eukaryotic 18S small subunit rRNA gene sequence has been useful in identifying apicomplexans in tetrapods, identification of apicomplexans infecting fishes has relied solely on morphological identification by microscopy. In this study, a DNA barcoding method was developed that targets the 18S rRNA gene primers for identifying apicomplexans parasitizing certain actinopterygian fishes. A lead primer set was selected showing no cross-reactivity to the overwhelming abundant host DNA and successfully confirmed 37 of the 41 (90.2%) microscopically verified parasitized fish blood samples analyzed in this study. Furthermore, this DNA barcoding method identified 4 additional samples that screened negative for parasitemia, suggesting this molecular method may provide improved sensitivity over morphological characterization by microscopy. In addition, this PCR screening method for fish apicomplexans, using Whatman FTA preserved DNA, was tested in efforts leading to a more simplified field collection, transport, and sample storage method as well as a streamlining sample processing important for DNA barcoding of large sample sets.

  9. A species-specific recognition system directs haustorium development in the parasitic plant Triphysaria (Scrophulariaceae).

    PubMed

    Yoder, J I

    1997-01-01

    Parasitic plants use host molecules to trigger development programs essential for parasitism. One such program governs the initiation, development, and function of haustoria, parasite-specific organs responsible for attachment and invasion of host tissues. Haustoria development can be initiated by several different molecules produced by appropriate host species. We are interested in understanding how these signals are interpreted by two related facultative parasites, Triphysaria eriantha (Benth). Chuang and Heckard, and T. versicolor Fischer and C. Meyer, to distinguish their own roots from those of potential hosts. We used an in vitro bioassay to determine what proportion of different Triphysaria populations formed haustoria in the presence and absence of closely related and unrelated host species. We found that the proportion of plants with haustoria was the same whether the plants were grown in isolation or with a conspecific host. In contrast, a significantly higher proportion of plants made haustoria when the host was a congeneric Triphysaria. Plants with haustoria neither enhanced nor inhibited other plants' propensity to form haustoria. Together these results indicate that qualitative differences exist in haustorium-inducing factors exuded by closely related species. The highest proportion of Triphysaria had haustoria when growth with Arabidopsis thaliana (L.) Heynh. Even in this case, however, some Triphysaria failed to develop haustoria. Interestingly, the percentage of haustoria that had vessel elements was higher when connections were made with Arabidopsis than with another Triphysaria. These results demonstrate that host recognition can be manifested at multiple points in haustorium development.

  10. The redox biology of schistosome parasites and applications for drug development.

    PubMed

    Huang, Hsin-Hung; Rigouin, Coraline; Williams, David L

    2012-01-01

    Schistosomiasis caused by Schistosoma spp. is a serious public health concern, especially in sub-Saharan Africa. Praziquantel is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Antioxidants are appealing drug targets. In order to survive in their hosts, schistosomes are challenged by reactive oxygen species from intrinsic and extrinsic sources. Schistosome antioxidant enzymes have been identified as essential proteins and novel drug targets and inhibition of the antioxidant response can lead to parasite death. Because the organization of the redox network in schistosomes is significantly different from that in humans, new drugs are being developed targeting schistosome antioxidants. In this paper the redox biology of schistosomes is discussed and their potential use as drug targets is reviewed. It is hoped that compounds targeting parasite antioxidant responses will become clinically relevant drugs in the near future.

  11. Development and validation of the random walk algorithm: application to the classification of diffuse heterogeneity in brain SPECT perfusion images.

    PubMed

    Modzelewski, Romain; de la Rue, Thierry; Janvresse, Elise; Hitzel, Anne; Menard, Jean François; Manrique, Alain; Gardin, Isabelle; Gerardin, Emmanuel; Hannequin, Didier; Vera, Pierre

    2008-01-01

    Heterogeneity analysis has been studied for radiological imaging, but few methods have been developed for functional images. Diffuse heterogeneous perfusion frequently appears in brain single photon emission computed tomography (SPECT) images, but objective quantification is lacking. An automatic method, based on random walk (RW) theory, has been developed to quantify perfusion heterogeneity. We assess the robustness of our algorithm in differentiating levels of diffuse heterogeneity even when focal defects are present. Heterogeneity is quantified by counting R (percentage), the mean rate of visited pixels in a fixed number of steps of the stochastic RW process. The algorithm has been tested on the numerical anthropomorphic Zubal head phantom. Seven diffuse cortical heterogeneity levels were simulated with an adjustable Gaussian function and 6 temporoparietal focal defects simulating Alzheimer Disease, leading to 42 phantoms. Data were projected and smoothed (full width at half maximum, 5.5 mm), and Poisson noise was added to the 64 projections. The SPECT data were reconstructed using filtered backprojection (Hamming filter, 0.5 c/p). R values for different levels of perfusion defect and diffuse heterogeneity were evaluated on 3 parameters: the number of slices studied (20 vs 40), the use of Talairach normalization versus original space, and the use of a cortical mask within the Talairach space. For each parameter, regression lines for heterogeneity and temporoparietal defect quantification were analyzed by covariance statistics. R values were also evaluated on SPECT images performed on 25 subjects with suspected focal dementia and on 15 normal controls. Scans were blindly ranked by 2 experienced nuclear physicians according to the degree of diffuse heterogeneity. Variability of R was smaller than 0.17% for repeated measurements. R was more particularly influenced by diffuse heterogeneity compared with focal perfusion defect. The Talairach normalization had a

  12. Intestinal parasitic infections amongst Orang Asli (indigenous) in Malaysia: has socioeconomic development alleviated the problem?

    PubMed

    Lim, Y A L; Romano, N; Colin, N; Chow, S C; Smith, H V

    2009-08-01

    Orang Asli are the indigenous minority peoples of peninsular Malaysia. Despite proactive socioeconomic development initiated by the Malaysian Government in upgrading the quality of life of the Orang Asli communities since 1978, they still remained poor with a current poverty rate of 76.9%. Poverty exacerbates the health problems faced by these communities which include malnourishment, high incidences of infectious diseases (eg. tuberculosis, leprosy, malaria) and the perpetual problem with intestinal parasitic infections. Studies reported that the mean infection rate of intestinal parasitic infections in Orang Asli communities has reduced from 91.1% in 1978, to 64.1% in the subsequent years. Although the results was encouraging, it has to be interpreted with caution because nearly 80% of studies carried out after 1978 still reported high prevalence (i.e. >50%) of soil-transmitted helminthiases (STH) among Orang Asli communities. Prior to 1978, hookworm infection is the most predominant STH but today, trichuriasis is the most common STH infections. The risk factors for intestinal parasitic infections remained unchanged and studies conducted in recent years suggested that severe STH infections contributed to malnutrition, iron deficiency anaemia and low serum retinol in Orang Asli communities. In addition, STH may also contribute to poor cognitive functions and learning ability. Improvements in socioeconomic status in Malaysia have shown positive impact on the reduction of intestinal parasitic infections in other communities however, this positive impact is less significant in the Orang Asli communities. In view of this, a national parasitic infections baseline data on morbidity and mortality in the 18 subgroups of Orang Asli, will assist in identifying intervention programmes required by these communities. It is hope that the adoption of strategies highlighted in the World Health Organisation- Healthy Village Initiatives (WHO-HVI) into Orang Asli communities will

  13. Exo-erythrocytic development of avian malaria and related haemosporidian parasites.

    PubMed

    Valkiūnas, Gediminas; Iezhova, Tatjana A

    2017-03-03

    Avian malaria parasites (Plasmodium spp.) and related haemosporidians (Haemosporida) are responsible for diseases which can be severe and even lethal in avian hosts. These parasites cause not only blood pathology, but also damage various organs due to extensive exo-erythrocytic development all over the body, which is not the case during Plasmodium infections in mammals. However, exo-erythrocytic development (tissue merogony or schizogony) remains the most poorly investigated part of life cycle in all groups of wildlife haemosporidian parasites. In spite of remarkable progress in studies of genetic diversity, ecology and evolutionary biology of avian haemosporidians during the past 20 years, there is not much progress in understanding patterns of exo-erythrocytic development in these parasites. The purpose of this review is to overview the main information on exo-erythrocytic development of avian Plasmodium species and related haemosporidian parasites as a baseline for assisting academic and veterinary medicine researchers in morphological identification of these parasites using tissue stages, and to define future research priorities in this field of avian malariology. The data were considered from peer-reviewed articles and histological material that was accessed in zoological collections in museums of Australia, Europe and the USA. Articles describing tissue stages of avian haemosporidians were included from 1908 to the present. Histological preparations of various organs infected with the exo-erythrocytic stages of different haemosporidian parasites were examined. In all, 229 published articles were included in this review. Exo-erythrocytic stages of avian Plasmodium, Fallisia, Haemoproteus, Leucocytozoon, and Akiba species were analysed, compared and illustrated. Morphological characters of tissue stages that can be used for diagnostic purposes were specified. Recent molecular studies combined with histological research show that avian haemosporidians are more

  14. The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development

    PubMed Central

    Zheng, Hong; Tan, Zhangping; Zhou, TaoLi; Zhu, Feng; Ding, Yan; Liu, Taiping; Wu, Yuzhang; Xu, Wenyue

    2015-01-01

    TLRs (Toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. Although several TLRs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of TLRs in the development of the pre-erythrocytic stage is still largely unknown. Here, we found that sporozoite and its lysate could significantly activate the TLR2, and induce macrophages to release proinflammatory cytokines, including IL-6, MCP-1 and TNF-α, in a TLR2-dependent manner. Further studies showed that sporozoite and its lysate could be recognized by either TLR2 homodimers or TLR2/1 and TLR2/6 heterodimers, implicating the complexity of TLR2 agonist in sporozoite. Interestingly, the TLR2 signaling can significantly suppress the development of the pre-erythrocytic stage of Plasmodium yoelii, as both liver parasite load and subsequent parasitemia were significantly elevated in both TLR2- and MyD88-deficient mice. Additionally, the observed higher level of parasite burden in TLR2−/− mice was found to be closely associated with a reduction in proinflammatory cytokines in the liver. Therefore, we provide the first evidence that sporozoites can activate the TLR2 signaling, which in turn significantly inhibits the intrahepatic parasites. This may provide us with novel clues to design preventive anti-malaria therapies. PMID:26667391

  15. Embryonic development period and the prevalence of avian blood parasites.

    PubMed Central

    Ricklefs, R E

    1992-01-01

    Variation in prevalence of avian hematozoa is related to taxonomic affiliation at the level of the family or subfamily but not of the genus within families. Prevalence is comparatively insensitive to the influences of habitat and season; however, temperate species have higher incidences of infection than tropical species belonging to the same families. Among taxa of nonraptorial altricial landbirds, hematozoan prevalence is inversely related to the length of the incubation period but shows little relationship to body size and rate of postnatal development. This finding suggests a possible link between the duration of embryonic development and the ability to resist or control infection, possibly due to maturational processes in the avian immune system. PMID:1584808

  16. Development of a novel two color tracer perfusion technique for the hydrodynamic study of aqueous outflow in bovine eyes

    PubMed Central

    Jing-yin, ZHU; Wen, YE; Hai-yan, GONG

    2010-01-01

    Background Elevation of intraocular pressure is usually associated with primary open angle glaucoma and caused by increased outflow resistance. A two-color fluorescent tracer technique was developed to investigate the hydrodynamics of aqueous humor outflow with changing intraocular pressure within the same eye, to better understand the relationship between outflow facility and effective filtration area. Methods Eighteen enucleated bovine eyes were first perfused at 30 mmHg with Dulbecco’s phosphate-buffered saline containing 5.5 mmol/L D-glucose. After a stable baseline facility, red fluorescent microspheres (0.5 μm, 0.002% v/v) were exchanged and perfused. Eyes in the one-color control group (n=6) were immediately perfused with fixative. In the experimental group (n=6), eyes were perfused with green tracer after intraocular pressure reduced to 7 mmHg, while in the two-color control group (n=6), eyes were perfused with green tracer with intraocular pressure remaining at 30 mmHg. All 12 eyes were then perfusion-fixed. Outflow facility was continuously recorded in all eyes. Confocal images were taken along the inner wall of the aqueous plexus and the percent of the effective filtration length (PEFL; length of inner wall exhibiting tracer labeling/total length of inner wall) was measured. The relationships between outflow facility and PEFL were analyzed statistically. Results No significant differences were found in baseline facilities (μl·min−1·mmHg−1) among the three groups (the experimental group: 0.93±0.12; the two-color control group: 0.90±0.19; the one-color control group: 0.98±0.13). In the experimental group, the outflow facility was significantly higher at 7 mmHg (4.29±1.01) than that at 30 mmHg (1.90±0.67, P <0.001), which corresponded to a significant increase in the PEFL at 7 mmHg (54.70±8.42) from that at 30 mmHg ((11.76±4.56)%, P <0.001). The PEFL labeled by red fluorescent microspheres in the experimental group ((11.76±4.56)%) showed

  17. Effects of parasitism by Asobara tabida (Hymenoptera: Braconidae) on the development, survival and activity of Drosophila melanogaster larvae.

    PubMed

    Moreau, S J.M.; Dingremont, A; Doury, G; Giordanengo, P

    2002-03-01

    The impact of parasitism by Asobara tabida on Drosophila melanogaster larval development, survival features and larval activity has been investigated using two strains of the parasitoid. The successful parasitism rate of the A1 strain was four times greater than that of the WOPV strain. Both strains induced equivalent mortality rates but hosts parasitized by A1 predominantly died as pupae. The time necessary for the host pupariation and emergence, and the larval weight at 72, 96 and 120 h post-parasitization were measured. Parasitized larvae exhibited longer periods of development and lower weights than controls, especially when parasitized by A1. These results suggest that hosts underwent physiological costs varying with respect to the outcome of the parasitic relationship. Of the parasitoid factors possibly responsible for these costs, we examined venoms for their impact on host mortality. Artificial injections of WOPV venoms induced higher mortality rates than did A1 venoms. Venoms were also found responsible for the induction of a transient paralysis, naturally occuring after parasitization. Again, the strongest effect was observed after parasitization by WOPV or injections of its venoms. This study gives new insights into the intriguing features of A. tabida and constitutes the first report of the paralysing properties of the venoms.

  18. Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites.

    PubMed

    Pearson, Mark S; Ranjit, Najju; Loukas, Alex

    2010-08-01

    Proteases are pivotal to parasitism, mediating biological processes crucial to worm survival including larval migration through tissue, immune evasion/modulation and nutrient acquisition by the adult parasite. In haematophagous parasites, many of these proteolytic enzymes are secreted from the intestine (nematodes) or gastrodermis (trematodes) where they act to degrade host haemoglobin and serum proteins as part of the feeding process. These proteases are exposed to components of the immune system of the host when the worms ingest blood, and therefore present targets for the development of anti-helminth vaccines. The protective effects of current vaccine antigens against nematodes that infect humans (hookworm) and livestock (barber's pole worm) are based on haemoglobin-degrading intestinal proteases and act largely as a result of the neutralisation of these proteases by antibodies that are ingested with the blood-meal. In this review, we survey the current status of helminth proteases that show promise as vaccines and describe their vital contribution to a parasitic existence.

  19. Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

    PubMed Central

    Gabrieli, Paolo; Buckee, Caroline O.; Catteruccia, Flaminia

    2016-01-01

    The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance. PMID:27977810

  20. Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes.

    PubMed

    Zhu, Feng; Liu, Taiping; Zhao, Chenhao; Lu, Xiao; Zhang, Jian; Xu, Wenyue

    2017-01-01

    As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection. The depletion of CD4(+) T cells prior to the adoptive transfer of parasites into WKV-immunized mice has no effect on the development of the malaria parasite in the mosquito, but the adoptive transfer of the serum from the immunized mice into the parasite-inoculated mice remarkably suppresses the development of malaria parasites in mosquitoes. Furthermore, immunized mice challenged with the malaria parasite generate higher levels of parasite-specific Abs and the inflammatory cytokines MCP-1 and IFN-γ. However, the adoptive transfer of parasite-specific IgG or the depletion of MCP-1, but not IFN-γ, to some extent is closely associated with the suppression of malaria parasite development in mosquitoes. These data strongly suggest that WKV-induced immune responses confer protection against the mosquito stage, which is largely dependent on malaria parasite-specific Abs and MCP-1. This finding sheds new light on blocking malaria transmission through the immunization of individuals with the WKV. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Developing vaccines to control protozoan parasites in ruminants: dead or alive?

    PubMed

    Innes, Elisabeth A; Bartley, Paul M; Rocchi, Mara; Benavidas-Silvan, Julio; Burrells, Alison; Hotchkiss, Emily; Chianini, Francesca; Canton, German; Katzer, Frank

    2011-08-04

    Protozoan parasites are among some of the most successful organisms worldwide, being able to live and multiply within a very wide range of hosts. The diseases caused by these parasites cause significant production losses in the livestock sector involving reproductive failure, impaired weight gain, contaminated meat, reduced milk yields and in severe cases, loss of the animal. In addition, some protozoan parasites affecting livestock such as Toxoplasma gondii and Cryptosporidium parvum may also be transmitted to humans where they can cause serious disease. Data derived from experimental models of infection in ruminant species enables the study of the interactions between parasite and host. How the parasite initiates infection, becomes established and multiplies within the host and the critical pathways that may lead to a disease outcome are all important to enable the rational design of appropriate intervention strategies. Once the parasites invade the hosts they induce both innate and adaptive immune responses and the induction and function of these immune responses are critical in determining the outcome of the infection. Vaccines offer green solutions to control disease as they are sustainable, reducing reliance on pharmacological drugs and pesticides. The use of vaccines has multiple benefits such as improving animal health and welfare by controlling animal infections and infestations; improving public health by controlling zoonoses and food borne pathogens in animals; solving problems associated with resistance to acaricides, antibiotics and anthelmintics; keeping animals and the environment free of chemical residues and maintaining biodiversity. All of these attributes should lead to improved sustainability of animal production and economic benefit. Using different protozoan parasitic diseases as examples this paper will discuss various approaches used to develop vaccines to protect against disease in livestock and discuss the relative merits of using live

  2. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture

    PubMed Central

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-01-01

    Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays. PMID:26669749

  3. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture.

    PubMed

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-12-16

    Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays.

  4. Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture

    NASA Astrophysics Data System (ADS)

    Huang, Song-Bin; Chou, Dean; Chang, Yu-Han; Li, Ke-Cing; Chiu, Tzu-Keng; Ventikos, Yiannis; Wu, Min-Hsien

    2015-12-01

    Before microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective, and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays.

  5. Micro-perfusion for cardiac tissue engineering: development of a bench-top system for the culture of primary cardiac cells.

    PubMed

    Khait, Luda; Hecker, Louise; Radnoti, Desmond; Birla, Ravi K

    2008-05-01

    Tissue-engineered constructs have high metabolic requirements during in vitro culture necessitating the development of micro-perfusion systems to maintain high functional performance. In this study, we describe the design, fabrication, and testing of a novel micro-perfusion system to support the culture of primary cardiac cells. Our system consists of a micro-incubator with independent stages for 35-mm tissue culture plates with inflow/outflow manifolds for fluid delivery and aspiration. A peristaltic pump is utilized for fluid delivery and vacuum for fluid aspiration. Oxygen saturation, pH, and temperature are regulated for the media while temperature is regulated within the micro-incubator, fluid reservoir, and oxygenation chamber. Validation of the perfusion system was carried out using primary cardiac myocytes, isolated from 2- to 3-day-old neonatal rat hearts, plated on collagen-coated tissue culture plates. Two million cells/plate were used and the perfusion system was run for 1 h (without the need for a cell culture incubator) while controls were maintained in a standard cell culture incubator. We evaluated the cell viability, cell adhesion, total protein, total RNA, and changes in the expression of SERCA2 and phospholamban using RT-PCR, with N = 6 for each group. We found that there was no significant change in any variable during the 1-h run in the perfusion system. These studies served to demonstrate the compatibility of the perfusion system to support short-term culture of primary cardiac cells.

  6. Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia

    PubMed Central

    Miyamoto, Yukiko; Eckmann, Lars

    2015-01-01

    Diarrheal diseases are among the leading causes of morbidity and mortality in the world, particularly among young children. A limited number of infectious agents account for most of these illnesses, raising the hope that advances in the treatment and prevention of these infections can have global health impact. The two most important parasitic causes of diarrheal disease are Cryptosporidium and Giardia. Both parasites infect predominantly the small intestine and colonize the lumen and epithelial surface, but do not invade deeper mucosal layers. This review discusses the therapeutic challenges, current treatment options, and drug development efforts against cryptosporidiosis and giardiasis. The goals of drug development against Cryptosporidium and Giardia are different. For Cryptosporidium, only one moderately effective drug (nitazoxanide) is available, so novel classes of more effective drugs are a high priority. Furthermore, new genetic technology to identify potential drug targets and better assays for functional evaluation of these targets throughout the parasite life cycle are needed for advancing anticryptosporidial drug design. By comparison, for Giardia, several classes of drugs with good efficacy exist, but dosing regimens are suboptimal and emerging resistance begins to threaten clinical utility. Consequently, improvements in potency and dosing, and the ability to overcome existing and prevent new forms of drug resistance are priorities in antigiardial drug development. Current work on new drugs against both infections has revealed promising strategies and new drug leads. However, the primary challenge for further drug development is the underlying economics, as both parasitic infections are considered Neglected Diseases with low funding priority and limited commercial interest. If a new urgency in medical progress against these infections can be raised at national funding agencies or philanthropic organizations, meaningful and timely progress is possible

  7. Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models.

    PubMed

    Salman, Ahmed M; Montoya-Díaz, Eduardo; West, Heather; Lall, Amar; Atcheson, Erwan; Lopez-Camacho, Cesar; Ramesar, Jai; Bauza, Karolis; Collins, Katharine A; Brod, Florian; Reis, Fernando; Pappas, Leontios; González-Cerón, Lilia; Janse, Chris J; Hill, Adrian V S; Khan, Shahid M; Reyes-Sandoval, Arturo

    2017-04-18

    Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation.

  8. Development of the isolated perfused porcine skin flap for in vitro studies of percutaneous absorption pharmacokinetics and cutaneous biotransformation

    SciTech Connect

    Carver, M.P.

    1988-01-01

    The isolated perfused porcine skin flap (IPPSF) has proven to be a valuable in vitro tool for studying the physiology and biochemistry of skin and for identifying biochemical and histological markers of direct cutaneous toxicity. The present experiments were undertaken for two purposes: (1) to develop a pharmacokinetic model, based on dermal penetration in the IPPSF, which is predictive of percutaneous absorption in vivo, and (2) to examine cutaneous biotransformation of the important agricultural poison parathion (P). Dosing solutions of {sup 14}C-radiolabelled compounds representing 3 chemical classes-organic acid/base (benzoic acid (B), caffeine (C)), organophosphate (OP) pesticides, and steroid hormones, were applied topically in ethanol at 40 {mu}m cm{sup {minus}2}, both in vivo and on the IPPSF. A 3-compartment pharmacokinetic model describing mass transfer from the surface (C{sub 1}), diffusion through epidermis and dermis (C{sub 2}), and transfer into the perfusate (C{sub 3}), was developed based on flux through the IPPSF from 0-8 hr. Model simulations were predictive of percutaneous absorption in vivo for the OP's and steroids. Modification of the basic 3-compartment model to account for fast and slow tissue-release processes (B) and for flux-dependent perfusage flow increases (C), provided excellent in vivo-in vitro correlation over all 7 compounds.

  9. Development of a Multispectral Tissue Characterization System for Optimization of an Implantable Perfusion Status Monitor for Transplanted Liver

    SciTech Connect

    Baba, Justin S; Letzen, Brian S; Ericson, Milton Nance; Cote, Gerard L.; Xu, Weijian; Wilson, Mark A.

    2009-01-01

    Optimizing wavelength selection for monitoring perfusion during liver transplant requires an in-depth characterization of liver optical properties. With these, the impact of liver absorption and scattering properties can be investigated to select optimal wavelengths for perfusion monitoring. To accomplish this, we are developing a single integrating-sphere-based using a unique spatially resolved diffuse reflectance system for optical properties determination for thick samples. We report early results using a monochromatic source implementation to measure the optical properties of well characterized tissue phantoms made from polystyrene spheres and Trypan blue. The presented results show the promise of using this unique system to measure the optical properties of the tissue phantoms. We are currently in the process of implementing an automated Levenberg Marquardt fitting algorithm to determine the peak location of the diffuse reflectance profile to ensure robust computation of sample optical properties. Future work will focus on the incorporation of multispectral capability to the technique to facilitate development of more realistic liver tissue phantoms.

  10. Transcriptome of Small Regulatory RNAs in the Development of the Zoonotic Parasite Trichinella spiralis

    PubMed Central

    Tang, Bin; Piao, Xianyu; Hou, Nan; Peng, Shuai; Jiang, Ning; Yin, Jigang; Liu, Mingyuan; Chen, Qijun

    2011-01-01

    Background Trichinella spiralis is a parasite with unique features. It is a multicellular organism but with an intracellular parasitization and development stage. T. spiralis is the helminthic pathogen that causes zoonotic trichinellosis and afflicts more than 10 million people worldwide, whereas the parasite's biology, especially the developmental regulation is largely unknown. In other organisms, small non-coding RNAs, such as microRNAs (miRNA) and small interfering RNAs (siRNA) execute post-transcriptional regulation by translational repression or mRNA degradation, and a large number of miRNAs have been identified in diverse species. In T. spiralis, the profile of small non-coding RNAs and their function remains poorly understood. Methodology and Principal Findings Here, the transcriptional profiles of miRNA and siRNA in three developmental stages of T. spiralis in the rat host were investigated, and compared by high-throughput cDNA sequencing technique (“RNA-seq”). 5,443,641 unique sequence tags were obtained. Of these, 21 represented conserved miRNAs related to 13 previously identified metazoan miRNA families and 213 were novel miRNAs so far unique to T. spiralis. Some of these miRNAs exhibited stage-specific expression. Expression of miRNAs was confirmed in three stages of the life cycle by qRT-PCR and northern blot analysis. In addition, endogenous siRNAs (endo-siRNAs) were found mainly derived from natural antisense transcripts (NAT) and transposable elements (TE) in the parasite. Conclusions and Significance We provide evidence for the presence of miRNAs and endo-siRNAs in T. spiralis. The miRNAs accounted for the major proportion of the small regulatory RNA population of T. spiralis, while fewer endogenous siRNAs were found. The finding of stage-specific expression patterns of the miRNAs in different developmental stages of T. spiralis suggests that miRNAs may play important roles in parasite development. Our data provide a basis for further

  11. Development and validation of a novel bioreactor system for load- and perfusion-controlled tissue engineering of chondrocyte-constructs.

    PubMed

    Schulz, Ronny M; Wüstneck, Nico; van Donkelaar, Corrinus C; Shelton, Julia C; Bader, Augustinus

    2008-11-01

    Osteoarthritis is a severe socio-economical disease, for which a suitable treatment modality does not exist. Tissue engineering of cartilage transplants is the most promising method to treat focal cartilage defects. However, current culturing procedures do not yet meet the requirements for clinical implementation. This article presents a novel bioreactor device for the functional tissue engineering of articular cartilage which enables cyclic mechanical loading combined with medium perfusion over long periods of time, under controlled cultivation and stimulation conditions whilst ensuring system sterility. The closed bioreactor consists of a small, perfused, autoclavable, twin chamber culture device with a contactless actuator for mechanical loading. Uni-axial loading is guided by externally applied magnetic fields with real-time feedback-control from a platform load cell and an inductive proximity sensor. This precise measurement allows the development of the mechanical properties of the cultured tissue to be monitored in real-time. This is an essential step towards clinical implementation, as it allows accounting for differences in the culture procedure induced by patient-variability. This article describes, based on standard agarose hydrogels of 3 mm height and 10 mm diameter, the technical concept, implementation, scalability, reproducibility, precision, and the calibration procedures of the whole bioreactor instrument. Particular attention is given to the contactless loading system by which chondrocyte scaffolds can be compressed at defined loading frequencies and magnitudes, whilst maintaining an aseptic cultivation procedure. In a "proof of principle" experiment, chondrocyte seeded agarose gels were cultured for 21 days in the bioreactor system. Intermittent medium perfusion at a steady flow rate (0.5 mL/min) was applied. Sterility and cell viability (ds-DNA quantification and fluorometric live/dead staining) were preserved in the system. Flow induced shear

  12. Artemisinin-Resistant Plasmodium falciparum Parasites Exhibit Altered Patterns of Development in Infected Erythrocytes

    PubMed Central

    Hott, Amanda; Casandra, Debora; Sparks, Kansas N.; Morton, Lindsay C.; Castanares, Geocel-Grace; Rutter, Amanda

    2015-01-01

    Artemisinin derivatives are used in combination with other antimalarial drugs for treatment of multidrug-resistant malaria worldwide. Clinical resistance to artemisinin recently emerged in southeast Asia, yet in vitro phenotypes for discerning mechanism(s) of resistance remain elusive. Here, we describe novel phenotypic resistance traits expressed by artemisinin-resistant Plasmodium falciparum. The resistant parasites exhibit altered patterns of development that result in reduced exposure to drug at the most susceptible stage of development in erythrocytes (trophozoites) and increased exposure in the most resistant stage (rings). In addition, a novel in vitro delayed clearance assay (DCA) that assesses drug effects on asexual stages was found to correlate with parasite clearance half-life in vivo as well as with mutations in the Kelch domain gene associated with resistance (Pf3D7_1343700). Importantly, all of the resistance phenotypes were stable in cloned parasites for more than 2 years without drug pressure. The results demonstrate artemisinin-resistant P. falciparum has evolved a novel mechanism of phenotypic resistance to artemisinin drugs linked to abnormal cell cycle regulation. These results offer insights into a novel mechanism of drug resistance in P. falciparum and new tools for monitoring the spread of artemisinin resistance. PMID:25779582

  13. The malarial serine protease SUB1 plays an essential role in parasite liver stage development.

    PubMed

    Suarez, Catherine; Volkmann, Katrin; Gomes, Ana Rita; Billker, Oliver; Blackman, Michael J

    2013-01-01

    Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. Whilst elements of liver stage merozoite biology are similar to those in the much better-studied blood stage merozoites, little is known of the molecular players involved in liver stage merozoite production. To facilitate the study of liver stage biology we developed a strategy for the rapid production of complex conditional alleles by recombinase mediated engineering in Escherichia coli, which we used in combination with existing Plasmodium berghei deleter lines expressing Flp recombinase to study subtilisin-like protease 1 (SUB1), a conserved Plasmodium serine protease previously implicated in blood stage merozoite maturation and egress. We demonstrate that SUB1 is not required for the early stages of intrahepatic growth, but is essential for complete development of the liver stage schizont and for production of hepatic merozoites. Our results indicate that inhibitors of SUB1 could be used in prophylactic approaches to control or block the clinically silent pre-erythrocytic stage of the malaria parasite life cycle.

  14. Equine immunity to parasites.

    PubMed

    Klei, T R

    2000-04-01

    Helminths are among the most significant parasites of horses in developed countries. This article examines immune responses against helminth parasites and the implications that immunologic investigations have on vaccine development, improvement of diagnostic procedures, and disease eradication.

  15. Invasion and egress by the obligate intracellular parasite Toxoplasma gondii: potential targets for the development of new antiparasitic drugs.

    PubMed

    Lavine, M D; Arrizabalaga, G

    2007-01-01

    Intracellular protozoan parasites are a great threat to animal and human health. To successfully disseminate through an organism these parasites must be able to enter and exit host cells efficiently and rapidly. The inhibition of invasion or egress of obligate intracellular parasites is regarded as a goal for drug development since these processes are essential for their survival and likely to require proteins unique to the parasites. Thus, a more comprehensive knowledge of invasion and egress proteins will aid in the development of drugs and vaccines against these intracellular pathogens. In recent years, the study of a particular parasite, Toxoplasma gondii, has yielded valuable information on how invasion and egress are achieved by some protozoan parasites. Besides being a good model system for the study of parasite biology, Toxoplasma is an important human pathogen capable of causing devastating disease in both immunocompromised individuals and developing fetuses. The lack of effective, inexpensive and tolerable drugs against Toxoplasma makes the development of new therapies an imperative. The following review describes how the identification and in depth study, using proteomics, forward genetics and pharmacology of the Toxoplasma proteins involved in entering and exiting human cells provide an important starting point in identifying targets for drug discovery.

  16. The Redox Biology of Schistosome Parasites and Applications for Drug Development

    PubMed Central

    Huang, Hsin-Hung; Rigouin, Coraline; Williams, David L.

    2013-01-01

    Schistosomiasis caused by Schistosoma spp. is a serious public health concern, especially in sub-Saharan Africa. Praziquantel is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Antioxidants are appealing drug targets. In order to survive in their hosts, schistosomes are challenged by reactive oxygen species from intrinsic and extrinsic sources. Schistosome antioxidant enzymes have been identified as essential proteins and novel drug targets and inhibition of the antioxidant response can lead to parasite death. Because the organization of the redox network in schistosomes is significantly different form that in humans, new drugs are being developed targeting schistosome antioxidants. In this paper the redox biology of schistosomes is discussed and their potential use as drug targets is reviewed. It is hoped that compounds targeting parasite antioxidant responses will become clinically relevant drugs in the near future. PMID:22607149

  17. Glutathione Reductase-null Malaria Parasites Have Normal Blood Stage Growth but Arrest during Development in the Mosquito*

    PubMed Central

    Pastrana-Mena, Rebecca; Dinglasan, Rhoel R.; Franke-Fayard, Blandine; Vega-Rodríguez, Joel; Fuentes-Caraballo, Mariela; Baerga-Ortiz, Abel; Coppens, Isabelle; Jacobs-Lorena, Marcelo; Janse, Chris J.; Serrano, Adelfa E.

    2010-01-01

    Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a γ-glutamylcysteine synthetase (γ-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for γ-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and γ-GCS by simultaneous disruption of gr and γ-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism. PMID:20573956

  18. Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito.

    PubMed

    Pastrana-Mena, Rebecca; Dinglasan, Rhoel R; Franke-Fayard, Blandine; Vega-Rodríguez, Joel; Fuentes-Caraballo, Mariela; Baerga-Ortiz, Abel; Coppens, Isabelle; Jacobs-Lorena, Marcelo; Janse, Chris J; Serrano, Adelfa E

    2010-08-27

    Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a gamma-glutamylcysteine synthetase (gamma-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for gamma-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and gamma-GCS by simultaneous disruption of gr and gamma-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism.

  19. Plasmodium vivax: ookinete destruction and oocyst development arrest are responsible for Anopheles albimanus resistance to circumsporozoite phenotype VK247 parasites.

    PubMed

    Gonzalez-Ceron, L; Rodriguez, M H; Santillan, F; Chavez, B; Nettel, J A; Hernandez-Avila, J E; Kain, K C

    2001-07-01

    Anopheles albimanus and An. pseudopunctipennis differ in their susceptibilities to Plasmodium vivax circumsporozoite phenotypes. An. pseudopunctipennis is susceptible to phenotype VK247 but almost refractory to VK210. In contrast, An. albimanus is almost refractory to VK247 but susceptible to VK210. To investigate the site in the mosquito and the parasite stage at which resistance mechanisms affect VK247 development in An. albimanus, parasite development was followed in a series of experiments in which both mosquitoes species were simultaneously infected with blood from patients. Parasite phenotype was determined in mature oocysts and salivary gland sporozoites by use of immunofluorescence and Western blot assays and/or gene identification. Ookinete maturation and their densities within the bloodmeal bolus were similar in both mosquito species. Ookinete densities on the internal midgut surface of An. albimanus were 4.7 times higher than those in An. pseudopunctipennis; however, the densities of developing oocysts on the external midgut surface were 6.12 times higher in the latter species. Electron microscopy observation of ookinetes in An. albimanus midgut epithelium indicated severe parasite damage. These results indicate that P. vivax VK247 parasites are destroyed at different parasite stages during migration in An. albimanus midguts. A portion, accumulated on the internal midgut surface, is probably destroyed by the mosquito's digestive enzymes and another portion is most likely destroyed by mosquito defense molecules within the midgut epithelium. A third group, reaching the external midgut surface, initiates oocyst development, but over 90% of them interrupt their development and die. The identification of mechanisms that participate in parasite destruction could provide new elements to construct transgenic mosquitoes resistant to malaria parasites.

  20. Structure and development of the upper haustorium in the parasitic flowering plant Cuscuta japonica (Convolvulaceae).

    PubMed

    Lee, Kyu Bae

    2007-05-01

    The anatomical and ultrastructural development of the haustorium of the Cuscuta japonica, a holoparasitic angiosperm, growing on the host plant Impatiens balsamina was studied. After the shoot tips of light-grown parasite seedlings contacted the host, the upper haustorium (external to the host organ) developed through three main successive stages of the haustorial initials, the meristem, and the endophyte primoridium (EP) within the middle layer of the cortex of the parasite stem. The haustorial initial cells were characterized by abundant starch-bearing amyloplasts and mitochondria with an expanded intermembrane space. The meristem cells had numerous large chloroplasts with well-developed thylakoids, reflecting the capability for photosynthesis. Commonly, all three stages of haustorial cells contained conspicuous, large nuclei with enlarged nucleoli and dense cytoplasm including many other organelles, indicating a very active metabolism. In the final stage of upper haustorium development, the meristem cells differentiated into the EP, a host-penetrating tissue. The primordium had smaller file cells at the proximal end and elongate digitate cells at the distal end. The file cells divided actively, while the digitate cells contained abundant chloroplasts, dictyosomes, rough endoplasmic reticulum, and other organelles, suggesting that the EP was cytohistologically well organized for penetration into the host tissue.

  1. [Development and application of information system for epidemiological investigation on parasitic diseases].

    PubMed

    Hu, Fei; Li, Yi-feng; Yuan, Min; Li, Jian-ying; Liu, Yue-min; Li, Zhao-jun; Lin, Dan-dan

    2014-10-01

    An information system for epidemiological investigation on parasitic diseases was developed. The foreground of this system was realized by using C# programming language, and the ACCESS database was used to implement the data management. The system was improved by continuous field application, and has been updated from version 1.0 to 3.0. The average treatment time, logic error rate, rate of sample loss, and post-processing error rate have now been reduced by 88.0%, 100%, 98.1%, and 100%, respectively (P<0.01). This system can reduce the human error and change the field investigation into effective and high-quality pattern.

  2. Development and Use of an X-ray Induced Fluorescence System Designed to Measure Regional Myocardial Perfusion

    DTIC Science & Technology

    1989-08-01

    Copenhaver , G.L., and Herr, M.D. In-vivo cardiac muscle perfusion: a new measurement method. IEEE Trans BME-34: 251-255, 1987. Mclnerney, J.J...Cliffs, New Jersey, 1975. Palmer, B.M., Mclnerney, J.J., Copenhaver , G.L., and Herr, M.D. Perfusion characteristics measured by X-ray fluorescence. Proc

  3. Nitric oxide blocks the development of the human parasite Schistosoma japonicum.

    PubMed

    Shen, Jia; Lai, De-Hua; Wilson, R Alan; Chen, Yun-Fu; Wang, Li-Fu; Yu, Zi-Long; Li, Mei-Yu; He, Ping; Hide, Geoff; Sun, Xi; Yang, Ting-Bao; Wu, Zhong-Dao; Ayala, Francisco J; Lun, Zhao-Rong

    2017-09-19

    Human schistosomiasis, caused by Schistosoma species, is a major public health problem affecting more than 700 million people in 78 countries, with over 40 mammalian host reservoir species complicating the transmission ecosystem. The primary cause of morbidity is considered to be granulomas induced by fertilized eggs of schistosomes in the liver and intestines. Some host species, like rats (Rattus norvegicus), are naturally intolerant to Schistosoma japonicum infection, and do not produce granulomas or pose a threat to transmission, while others, like mice and hamsters, are highly susceptible. The reasons behind these differences are still a mystery. Using inducible nitric oxide synthase knockout (iNOS(-/-)) Sprague-Dawley rats, we found that inherent high expression levels of iNOS in wild-type (WT) rats play an important role in blocking growth, reproductive organ formation, and egg development in S. japonicum, resulting in production of nonfertilized eggs. Granuloma formation, induced by fertilized eggs in the liver, was considerably exacerbated in the iNOS(-/-) rats compared with the WT rats. This inhibition by nitric oxide acts by affecting mitochondrial respiration and energy production in the parasite. Our work not only elucidates the innate mechanism that blocks the development and production of fertilized eggs in S. japonicum but also offers insights into a better understanding of host-parasite interactions and drug development strategies against schistosomiasis.

  4. Exploiting the Evolutionary Relationship between Malarial Parasites and Plants To Develop New Herbicides.

    PubMed

    Corral, Maxime G; Leroux, Julie; Tresch, Stefan; Newton, Trevor; Stubbs, Keith A; Mylne, Joshua S

    2017-08-07

    Herbicide resistance is driving a need to develop new herbicides. The evolutionary relationship between apicomplexan parasites, such as those causing malaria, and plants is close enough that many antimalarial drugs are herbicidal and so represent novel scaffolds for herbicide development. Using a compound library from the Medicines for Malaria Venture, the model plant Arabidopsis thaliana, and a physicochemical database of known herbicides, a compound was discovered that showed post-emergence herbicidal activity equal to commercial herbicides. Using structure-activity analysis, important points for its potency were found. The compound was also tested and found to be active against common crop weeds. Physiological profiling suggested the compound was a photosystem II inhibitor, representing a new scaffold for herbicide development. Overall this approach demonstrates the viability of using antimalarial compounds as lead compounds for the development of much needed new herbicides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Development of lymphatic filarial parasite Wuchereria bancrofti (Spirurida: Onchocercidae) in mosquito species (Diptera: Culicidae) fed artificially on microfilaremic blood.

    PubMed

    Paily, K P; Hoti, S L; Balaraman, K

    2006-11-01

    The efficiency of laboratory colonies of mosquitoes such as Anopheles stephensi Liston, Aedes aegypti (L.) Liverpool strain, Ae. aegypti wild type, Aedes albopictus (Skuse), Culex tritaeniorhynchus Giles, Culex sitiens Wiedemann, and Armigeres subalbatus Coquillett in supporting the development of Wuchereria bancrofti (Cobbold) (Spirurida: Onchocercidae) microfilariae to infective larvae was investigated. The mosquitoes were fed on heparinized microfilaremic human blood by using a membrane-feeding unit with Parafilm as membrane. The rate of infection, parasite development, and parasite burden were compared with that in the known vector mosquito Culex quinquefasciatus Say. Cx. quinquefasciatus showed the highest percentage of infection, followed by Ae. aegypti Liverpool strain and An. stephensi. The rate of development of the parasite was more or less similar in all the three species, and infective larvae were found on day 13. When the larvae were harvested on day 17, Cx. quinquefasciatus yielded the highest numbers, followed by Ae. aegypti Liverpool strain and An. stephensi. The percentage of infection was low, and the development was slow in Cx. tritaeniorhynchus compared with the other susceptible species. The parasite developed to second-stage larvae only by day 22 and to infective larvae by day 28. When 2-wk-old Cx. tritaeniorhynchus were fed on microfilaremic blood, they could develop the parasite to infective larvae by day 13 postfeeding. All other species of mosquitoes tested were found to be refractory to parasite development. It is shown that Cx. quinquefasciatus is the most suitable mosquito host for the production of infective larvae. However, Ae. aegypti Liverpool strain, which is commonly used for Brugia malayi filarial parasite, also can be used for generation of W. bancrofti infective larvae to circumvent the problem of maintaining two mosquito species.

  6. Pf332-C231-reactive antibodies affect growth and development of intra-erythrocytic Plasmodium falciparum parasites.

    PubMed

    Balogun, Halima A; Awah, Nancy W; Farouk, Salah E; Berzins, Klavs

    2011-12-09

    The Plasmodium falciparum antigen 332 (Pf332), is a megadalton parasite protein expressed at the surface of infected red cells during later stages of the parasite's developmental cycle. Antibodies to different parts of this antigen have been shown to inhibit parasite growth and adherence to host cells with or without ancillary cells. However, the mechanisms involved in these inhibitions remain largely unknown. We further analysed the activities of specific antibodies with regard to their specific mechanisms of action. For these analyses, affinity purified human antibodies against epitopes in the C-terminal fragment of Pf332 (Pf332-C231) were employed. All purified antibodies recognized Pf332-C231 both by immunofluorescence and ELISA. IgG was the main antibody isotype detected, although all sera investigated had varying proportions of IgG and IgM content. All the antibodies showed a capacity to inhibit parasite growth in P. falciparum cultures to different extents, mainly by acting on the more mature parasite stages. Morphological analysis revealed the antibody effects to be characterized by the presence of a high proportion of abnormal schizonts (15-30%) and pyknotic parasites. There was also an apparent antibody effect on the red cell integrity, as many developing parasites (up to 10% of trophozoites and schizonts) were extracellular. In some cases, the infected red cells appeared to be disintegrating/fading, staining paler than surrounding infected and uninfected cells. Antigen reversal of inhibition confirmed that these inhibitions were antigen specific. Furthermore, the growth of parasites after 22-42h exposure to antibodies was investigated. Following the removal of antibody pressure, a decreased growth rate of these parasites was seen compared to that of control parasites. The present study confirms the potential of Pf332 as a target antigen for parasite neutralizing antibodies, and further indicates that epitopes within the C231 region of Pf332 should

  7. Genes encoding homologous antigens in taeniid cestode parasites: Implications for development of recombinant vaccines produced in Escherichia coli.

    PubMed

    Gauci, Charles; Lightowlers, Marshall W

    2013-01-01

    Recombinant vaccine antigens are being evaluated for their ability to protect livestock animals against cysticercosis and related parasitic infections. Practical use of some of these vaccines is expected to reduce parasite transmission, leading to a reduction in the incidence of neurocysticercosis and hydatid disease in humans. We recently showed that an antigen (TSOL16), expressed in Escherichia coli, confers high levels of protection against Taenia solium cysticercosis in pigs, which provides a strategy for control of T. solium parasite transmission. Here, we discuss the characteristics of this antigen that may affect the utility of TSOL16 and related antigens for development as recombinant vaccines. We also report that genes encoding antigens closely related to TSOL16 from T. solium also occur in other related species of parasites. These highly homologous antigens have the potential to be used as vaccines and may provide protection against related species of Taenia that cause infection in other hosts.

  8. Molecular characterization of host-parasite cell signalling in Schistosoma mansoni during early development

    PubMed Central

    Ressurreição, Margarida; Elbeyioglu, Firat; Kirk, Ruth S.; Rollinson, David; Emery, Aidan M.; Page, Nigel M.; Walker, Anthony J.

    2016-01-01

    During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The ‘somules’ next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such ‘transactivation’ by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface. Further, we provide evidence that support the existence of specialized signalling domains called lipid rafts in schistosomes and propose that correct signalling to ERK requires proper raft organization. Finally, we show that modulation of PKC and ERK activities in somules affects motility and reduces somule survival. Thus, PKC and ERK are important mediators of host-ligand regulated transactivation events in schistosomes, and represent potential targets for anti-schistosome therapy aimed at reducing parasite survival in the human host. PMID:27762399

  9. Role of Insulin-Stimulated Adipose Tissue Perfusion in the Development of Whole-Body Insulin Resistance.

    PubMed

    Emanuel, Anna L; Meijer, Rick I; Muskiet, Marcel H A; van Raalte, Daniël H; Eringa, Etto C; Serné, Erik H

    2017-03-01

    After food ingestion, macronutrients are transported to and stored in the skeletal muscle and adipose tissue. They can be subsequently used as an energy source in times of energy deprivation. Uptake of these nutrients in myocytes and adipocytes depends largely on adequate tissue perfusion. Interestingly, insulin is able to dilate skeletal muscle arterioles, which facilitates the delivery of macronutrients and insulin itself to muscle tissue. Insulin-stimulated skeletal muscle perfusion is impaired in several insulin-resistant states and is believed to contribute to impaired skeletal muscle glucose uptake and consequently impaired whole-body glucose disposal. Insulin-resistant individuals also exhibit blunted postprandial adipose tissue perfusion. However, the relevance of this impairment to metabolic dysregulation is less clear. In this review, we provide an overview of adipose tissue perfusion in healthy and insulin-resistant individuals, its regulation among others by insulin, and the possible influences of impaired adipose tissue perfusion on whole-body insulin sensitivity. Finally, we propose a novel hypothesis that acute overfeeding impacts distribution of macronutrients by reducing skeletal muscle perfusion, while adipose tissue perfusion remains intact. An online visual overview is available for this article. © 2017 American Heart Association, Inc.

  10. Differential Subcellular Localization of Leishmania Alba-Domain Proteins throughout the Parasite Development

    PubMed Central

    Dupé, Aurélien; Dumas, Carole; Papadopoulou, Barbara

    2015-01-01

    Alba-domain proteins are RNA-binding proteins found in archaea and eukaryotes and recently studied in protozoan parasites where they play a role in the regulation of virulence factors and stage-specific proteins. This work describes in silico structural characterization, cellular localization and biochemical analyses of Alba-domain proteins in Leishmania infantum. We show that in contrast to other protozoa, Leishmania have two Alba-domain proteins, LiAlba1 and LiAlba3, representative of the Rpp20- and the Rpp25-like eukaryotic subfamilies, respectively, which share several sequence and structural similarities but also important differences with orthologs in other protozoa, especially in sequences targeted for post-translational modifications. LiAlba1 and LiAlba3 proteins form a complex interacting with other RNA-binding proteins, ribosomal subunits, and translation factors as supported by co-immunoprecipitation and sucrose gradient sedimentation analysis. A higher co-sedimentation of Alba proteins with ribosomal subunits was seen upon conditions of decreased translation, suggesting a role of these proteins in translational repression. The Leishmania Alba-domain proteins display differential cellular localization throughout the parasite development. In the insect promastigote stage, Alba proteins co-localize predominantly to the cytoplasm but they translocate to the nucleolus and the flagellum upon amastigote differentiation in the mammalian host and are found back to the cytoplasm once amastigote differentiation is completed. Heat-shock, a major signal of amastigote differentiation, triggers Alba translocation to the nucleolus and the flagellum. Purification of the Leishmania flagellum confirmed LiAlba3 enrichment in this organelle during amastigote differentiation. Moreover, partial characterization of the Leishmania flagellum proteome of promastigotes and differentiating amastigotes revealed the presence of other RNA-binding proteins, as well as differences in

  11. An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

    PubMed Central

    Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John

    2016-01-01

    BACKGROUND Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. OBJECTIVE The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. DESIGN A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. SETTING Multicentre study involving all five UK officially designated NHS adult lung transplant centres. PARTICIPANTS Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. INTERVENTION The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. MAIN OUTCOME MEASURES The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. RESULTS Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital

  12. In vitro development of Haemoproteus columbae (Haemosporida: Haemoproteidae), with perspectives for genomic studies of avian haemosporidian parasites.

    PubMed

    Coral, Arelis A; Valkiūnas, Gediminas; González, Angie D; Matta, Nubia E

    2015-10-01

    The evolutionary origin of wildlife and human malaria parasites (Plasmodium spp.) has been discussed for several decades. The lack of genomic data about species of wildlife haemosporidian parasites related to Plasmodium limits the number of taxa available for phylogenetic analysis. Genomic data about avian parasites of the genus Haemoproteus parasites, the sister genus to Plasmodium are still not available, mainly due to difficulties in obtaining pure DNA of parasites inhabiting nucleated avian host cells. Recent studies show that microgametes of Haemoproteus (Parahaemoproteus) spp. develop in vitro and can be isolated by simple centrifugation, allowing the isolation of pure parasite DNA for genomic studies. However, in vitro development of Haemoproteus (Haemoproteus) spp. has not been investigated, and it is unclear if microgametes of these parasites also can be obtained under in vitro conditions. Here, we provide the first data about the in vitro development of Haemoproteus (Haemoproteus) columbae, a widespread avian haemosporidian parasite, which is specific to pigeons and doves (Columbiformes) and is transmitted by hippoboscid flies (Diptera, Hippoboscidae). In vitro gametogenesis and ookinete development of H. columbae were studied using a strain isolated from a feral Rock Pigeon (Columba livia) in Bogotá-Colombia. The morphological events leading to exflagellation, fertilization and ookinete formation, as well as the rate of development of these stages were followed in vitro at 40 °C, 19 °C and 15 °C for 48 h. Macrogametes, microgametes, zygotes and initial stages of ookinete development were observed in all temperatures, but mature ookinetes were seen only at 40 °C. The largest diversity of sporogonic stages of H. columbae were present at 40 °C however, exflagellation, fertilization of macrogametes and development of immature ookinetes were also observed at 15 °C and 19 °C. Morphological and morphometric features of these stages in vitro were

  13. Selenophene and thiophene-core estrogen receptor ligands that inhibit motility and development of parasitic stages of Haemonchus contortus.

    PubMed

    Preston, Sarah; Luo, Junjie; Zhang, Yuezhou; Jabbar, Abdul; Crawford, Simon; Baell, Jonathan; Hofmann, Andreas; Hu, Min; Zhou, Hai-Bing; Gasser, Robin B

    2016-06-16

    Parasitic worms represent a substantial disease burden in animals and humans worldwide. The control of parasitic roundworms (nematodes) relies heavily on the use of anthelmintic drugs. However, widespread drug resistance in nematodes seriously compromises the effectiveness of many anthelmintics around the world. Thus, there is a need to discover new drugs, with unique modes of action, against parasites. Here, we synthesised and tested 74 selective estrogen receptor modulators (SERMs) for in vitro-activity on parasitic larvae of Haemonchus contortus (barber's pole worm), one of the most important nematode pathogens of small ruminants (including sheep and goats) and a key representative of one of the largest groups of parasitic nematodes (the Strongylida) of animals. We also studied the morphology of treated and untreated larvae using scanning electron microscopy (SEM), and assessed the agonistic/antagonistic activity of SERMs in a human embryonic kidney cell line using a luciferase reporter assay system. We identified three SERMs (one selenophene and two thiophene-core compounds) with potent inhibitory activities (at 3-25 μM) on the motility and development of parasitic stages of H. contortus. An SEM examination of treated H. contortus revealed considerable damage to the cuticle of fourth- but not exsheathed, third-stage larvae; this damage appeared to be consistent with that observed upon treatment with monepantel but not moxidectin (control compounds). The potency of the three SERMs compared favourably with commercially available anthelmintics, such that they warrant further assessment as nematocides. Future studies could focus on assessing the selectivity of these SERMs to parasites, characterising their target(s) and/or designing analogs that are parasite-specific.

  14. Does machine perfusion decrease ischemia reperfusion injury?

    PubMed

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival.

  15. Extension materials for meat-borne parasitic diseases in developing countries.

    PubMed

    Rimm, Mogens

    2003-06-01

    In support of a project on porcine cysticercosis in Tanzania, an educational video was prepared to inform the rural communities on the health risks and prevention of the parasitic disease. This paper describes the process involved in making the video, especially the importance of establishing a good understanding between veterinary public health officials and the video producer. Important steps in the process include determining the target audience, the film's core message, the construction of the "story", script development, the filming and editing activities, and, importantly, the development of strategies for production and use of the film as extension material. Suggestions on logistical and technical aspects of filming and viewing are also discussed. The experience gained in Tanzania will be of value to others planning similar projects elsewhere.

  16. Eimeria tenella: parasite-specific incorporation of /sup 3/H-uracil as a quantitative measure of intracellular development

    SciTech Connect

    Schmatz, D.M.; Crane, M.S.; Murray, P.K.

    1986-02-01

    An assay has been developed using parasite-specific incorporation of /sup 3/H-uracil to assess the intracellular growth of Eimeria tenella in vitro. As shown by both scintillation counts and autoradiography, /sup 3/H-uracil was incorporated specifically into intracellular parasites from the onset of infection and continued throughout development of the first generation schizonts. Mature schizonts and first generation merozoites did not continue to incorporate additional /sup 3/H-uracil, indicating that RNA synthesis had halted in these stages. Based on these findings, a semi-automated microscale uracil incorporation assay was developed to determine parasite viability. This method should be useful for biochemical studies with intracellular parasites and for screening compounds for anticoccidial activity. The ease, rapidity, and quantitative nature of this assay contrasts favorably with standard morphometric approaches of determining parasite development. In addition, parallel studies using host cell incorporation of /sup 3/H-uridine have been introduced as a method of determining whether antiparasitic activity is direct or indirect in relation to effects on the host cell.

  17. Tick vitellogenin receptor reveals critical role in oocyte development and transovarial transmission of Babesia parasite.

    PubMed

    Boldbaatar, Damdinsuren; Battsetseg, Badgar; Matsuo, Tomohide; Hatta, Takeshi; Umemiya-Shirafuji, Rika; Xuan, Xuenan; Fujisaki, Kozo

    2008-08-01

    A cDNA encoding the vitellogenin receptor of the ixodid tick, Haemaphysalis longicornis Neumann (HlVgR) was cloned and characterized. The full-length cDNA is 5631 bp, including an intact ORF encoding an expected protein with 1782 amino acids. The deduced amino acid sequence of the HlVgR cDNA revealed two ligand-binding domains with four class A cysteine-rich repeats in the first domain and eight in the second domain similar to those of insect VgRs. The immunoblot analysis detected approximately 197 kDa protein in both tick ovary and egg. The developmental expression profile demonstrated that HlVgR mRNA exists throughout the ovarian development, and the transcriptional level is especially high in the previtellogenic period. Immuno electron microscopy analysis demonstrated that the localization of HlVgR is detected on the external surface of oocyte plasma membrane. RNAi showed that eggs of HlVgR dsRNA-injected adult ticks had not developed into fully mature oocytes and laid abnormal eggs. The Babesia parasite DNA was not detected in the eggs of HlVgR dsRNA-injected tick that fed on Babesia gibsoni infected dog, whereas it was detected in the eggs of PBS-injected ticks and noninjected ticks. Expression of HlVgR was increased by the vitellogenic hormone 20-hydroxyecdysone. These results indicate that HlVgR, which is produced by the developing oocytes, is essential for Vg uptake, egg development in the H. longicornis tick, and transovarial transmission of Babesia parasites.

  18. Antibodies raised against hemolymph of Anopheles culicifacies reduce the fecundity and malaria parasite development.

    PubMed

    Kumari, Amrita; Gakhar, S K; Hooda, Vikas

    2009-12-01

    Several studies have been made to study the effect of antisera raised against different tissues (hemolymh, ovary, midgut and salivary glands) on the fecundity and malaria parasite development in the different species of mosquitoes but there are no reports on the antisera raised against the hemolymph of Anopheles culicifacies, the principal malaria vector in India accounting for 65% of malaria cases. Hence, an attempt was made to study the same and evaluate its impact on malaria parasite development. Polyclonal and multifactorial antibodies were produced in rabbits against heterogenous mixture of hemolymph proteins. Antibodies against hemolymph proteins were screened for their potential to influence reproductive performance of mosquitoes. Antibody titer in rabbit serum was determined by ELISA and putative candidate antigens were identified in the hemolymph of An. culicifacies by western blotting. Cross reactivity amongst various tissues vis-a-vis hemolymph protein was also identified. In addition, a significant reduction in oocyst development was also observed in An. culicifacies mosquitoes that ingested antihemolymph antibodies along with Plasmodium vivax. The maximum reduction in fecundity (57%) was observed during fourth week, after the last booster and number of oocyts per infected mosquito reduced by 73.35% in the group of mosquitoes that ingested antihemolymph antibodies along with the infected blood meal respectively. However, the ingestion of antibodies against hemolymph proteins did not have significant influence on hatchability. Antisera raised against hemolymph proteins of An. culicifacies recognized 11 polypeptides by western blotting. During the present study, 11 putative candidate antigens were identified in the hemolymph of An. culicifacies, against which antibodies produced significantly reduced the fecundity by 57%. In addition, a significant reduction in oocyst development was also observed in An. culicifacies that ingested antihemolymph antibodies

  19. Parasitism by Nycteribiidae and Streblidae Flies (Diptera) of a Malagasy Fruit Bat (Pteropodidae): Effects of Body Size and Throat Gland Development on Parasite Abundance.

    PubMed

    Rajemison, Faneva I; Noroalintseheno Lalarivoniaina, Oliva S; Goodman, Steven M

    2017-07-01

    We examined the possible effects of host body size and throat gland development on the abundance of blood-feeding nycteribiid and streblid flies parasitizing a Malagasy fruit bat, Rousettus madagascariensis G. Grandidier, 1928. Data were collected in the Parc National d'Ankarana in northern Madagascar during four visits: September 2014, 2015 (dry season), and January 2015, 2016 (wet season). Two bat fly species were identified, Eucampsipoda madagascarensis Theodor, 1955 (Nycteribiidae) and Megastrebla wenzeli (Jobling, 1952) (Streblidae). A positive correlation was found between host body size and abundance of E. madagascarensis during the four visits, suggesting that larger hosts have more parasites, and for M. wenzeli, this relationship was identified only during the wet season visits. In male hosts, body size and throat gland development are correlated with variation in E. madagascarensis abundance during the two seasons; this relationship was not found for M. wenzeli. We present some explanations for the observed patterns of bat fly abundance associated with throat gland development: increased vascularization and easier access to bloodmeals, chemical properties of gland secretions acting as attractants or perhaps being consumed, and modification of hair around the gland providing protection from bat grooming. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Shifts in the life history of parasitic wasps correlate with pronounced alterations in early development.

    PubMed

    Grbić, M; Strand, M R

    1998-02-03

    Developmental processes have been traditionally viewed to be invariant within higher taxa. However, examples are known whereby closely related species exhibit alterations in early embryogenesis yet appear very similar as adults. Such developmental changes are thought to occur in response to shifts in life history. In insects, the regulation of embryonic development has been intensively studied in model species like Drosophila melanogaster. Previous comparative studies suggest that the developmental processes documented in Drosophila well describe embryogenesis of advanced, holometabolous, insects generally. There have been few attempts, however, to take into account how life history has influenced early development of insects or to characterize early development of species with life histories fundamentally different from flies. Here we compared early development of two species from the same family of parasitic wasps that exhibit very different life histories. Bracon hebetor is an ectoparasite that lays large, yolky eggs on the integument of its host that develop much like the free-living honeybee and Drosophila. In contrast, Aphidius ervi is an endoparasite that lays small and apparently yolk-free eggs that develop in the hemocoel of the host. This wasp exhibits a radically different mode of early development at both the cellular and molecular level from B. hebetor. The developmental changes in A. ervi reflect functional adaptations for its derived life history and argue that departures from the fly paradigm may occur commonly among insects whose eggs develop under conditions different from typical terrestrial species.

  1. Shifts in the life history of parasitic wasps correlate with pronounced alterations in early development

    PubMed Central

    Grbic, Miodrag; Strand, Michael R.

    1998-01-01

    Developmental processes have been traditionally viewed to be invariant within higher taxa. However, examples are known whereby closely related species exhibit alterations in early embryogenesis yet appear very similar as adults. Such developmental changes are thought to occur in response to shifts in life history. In insects, the regulation of embryonic development has been intensively studied in model species like Drosophila melanogaster. Previous comparative studies suggest that the developmental processes documented in Drosophila well describe embryogenesis of advanced, holometabolous, insects generally. There have been few attempts, however, to take into account how life history has influenced early development of insects or to characterize early development of species with life histories fundamentally different from flies. Here we compared early development of two species from the same family of parasitic wasps that exhibit very different life histories. Bracon hebetor is an ectoparasite that lays large, yolky eggs on the integument of its host that develop much like the free-living honeybee and Drosophila. In contrast, Aphidius ervi is an endoparasite that lays small and apparently yolk-free eggs that develop in the hemocoel of the host. This wasp exhibits a radically different mode of early development at both the cellular and molecular level from B. hebetor. The developmental changes in A. ervi reflect functional adaptations for its derived life history and argue that departures from the fly paradigm may occur commonly among insects whose eggs develop under conditions different from typical terrestrial species. PMID:9448291

  2. Parasitic Diseases

    MedlinePlus

    ... a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  3. Development of 4D mathematical observer models for the task-based evaluation of gated myocardial perfusion SPECT.

    PubMed

    Lee, Taek-Soo; Frey, Eric C; Tsui, Benjamin M W

    2015-04-07

    This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of (99m)Tc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman's rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the

  4. Development of 4D mathematical observer models for the task-based evaluation of gated myocardial perfusion SPECT

    NASA Astrophysics Data System (ADS)

    Lee, Taek-Soo; Frey, Eric C.; Tsui, Benjamin M. W.

    2015-04-01

    This paper presents two 4D mathematical observer models for the detection of motion defects in 4D gated medical images. Their performance was compared with results from human observers in detecting a regional motion abnormality in simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D mathematical observer model extends the conventional channelized Hotelling observer (CHO) based on a set of 2D spatial channels and the second is a proposed model that uses a set of 4D space-time channels. Simulated projection data were generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16 gates/cardiac cycle. The activity distribution modelled uptake of 99mTc MIBI with normal perfusion and a regional wall motion defect. An analytical projector was used in the simulation and the filtered backprojection (FBP) algorithm was used in image reconstruction followed by spatial and temporal low-pass filtering with various cut-off frequencies. Then, we extracted 2D image slices from each time frame and reorganized them into a set of cine images. For the first model, we applied 2D spatial channels to the cine images and generated a set of feature vectors that were stacked for the images from different slices of the heart. The process was repeated for each of the 1,024 noise realizations, and CHO and receiver operating characteristics (ROC) analysis methodologies were applied to the ensemble of the feature vectors to compute areas under the ROC curves (AUCs). For the second model, a set of 4D space-time channels was developed and applied to the sets of cine images to produce space-time feature vectors to which the CHO methodology was applied. The AUC values of the second model showed better agreement (Spearman’s rank correlation (SRC) coefficient = 0.8) to human observer results than those from the first model (SRC coefficient = 0.4). The agreement with human observers indicates the proposed 4D mathematical observer model provides a good predictor of the

  5. An ex vivo comparison of adenosine and lidocaine solution and University of Wisconsin solution for hypothermic machine perfusion of porcine kidneys: potential for development.

    PubMed

    Hamaoui, Karim; Aftab, Adeel; Gowers, Sally; Boutelle, Martyn; Cook, Terry; Rudd, Donna; Dobson, Geoffrey P; Papalois, Vassilios

    2017-02-01

    The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca(2+), 16 mM Mg(2+), and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg; P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Inhibition of Protein Synthesis and Malaria Parasite Development by Drug Targeting of Methionyl-tRNA Synthetases

    PubMed Central

    Hussain, Tahir; Yogavel, Manickam

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRScyt and PfMRSapi. Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRScyt) or proteobacteria/primitive bacteria (PfMRSapi). We show that PfMRScyt localizes in parasite cytoplasm, while PfMRSapi localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several “hit” compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with 35S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. PMID:25583729

  7. Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases.

    PubMed

    Hussain, Tahir; Yogavel, Manickam; Sharma, Amit

    2015-04-01

    Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several "hit" compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Trypanosoma cruzi Immune Response Modulation Decreases Microbiota in Rhodnius prolixus Gut and Is Crucial for Parasite Survival and Development

    PubMed Central

    Castro, Daniele P.; Moraes, Caroline S.; Gonzalez, Marcelo S.; Ratcliffe, Norman A.; Azambuja, Patrícia; Garcia, Eloi S.

    2012-01-01

    Trypanosoma cruzi in order to complete its development in the digestive tract of Rhodnius prolixus needs to overcome the immune reactions and microbiota trypanolytic activity of the gut. We demonstrate that in R. prolixus following infection with epimastigotes of Trypanosoma cruzi clone Dm28c and, in comparison with uninfected control insects, the midgut contained (i) fewer bacteria, (ii) higher parasite numbers, and (iii) reduced nitrite and nitrate production and increased phenoloxidase and antibacterial activities. In addition, in insects pre-treated with antibiotic and then infected with Dm28c, there were also reduced bacteria numbers and a higher parasite load compared with insects solely infected with parasites. Furthermore, and in contrast to insects infected with Dm28c, infection with T. cruzi Y strain resulted in a slight decreased numbers of gut bacteria but not sufficient to mediate a successful parasite infection. We conclude that infection of R. prolixus with the T. cruzi Dm28c clone modifies the host gut immune responses to decrease the microbiota population and these changes are crucial for the parasite development in the insect gut. PMID:22574189

  9. Prolyl 4-Hydroxlase Activity Is Essential for Development and Cuticle Formation in the Human Infective Parasitic Nematode Brugia malayi*

    PubMed Central

    Winter, Alan D.; McCormack, Gillian; Myllyharju, Johanna; Page, Antony P.

    2013-01-01

    Collagen prolyl 4-hydroxylases (C-P4H) are required for formation of extracellular matrices in higher eukaryotes. These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4-hydroxyproline, a modification essential for the stability of the final triple helix. C-P4H are most often oligomeric complexes, with enzymatic activity contributed by the α subunits, and the β subunits formed by protein disulfide isomerase (PDI). Here, we characterize this enzyme class in the important human parasitic nematode Brugia malayi. All potential C-P4H subunits were identified by detailed bioinformatic analysis of sequence databases, function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans, whereas biochemical activity and complex formation were examined via co-expression in insect cells. Simultaneous RNAi of two B. malayi C-P4H α subunit-like genes resulted in a striking, highly penetrant body morphology phenotype in parasite larvae. This was replicated by single RNAi of a B. malayi C-P4H β subunit-like PDI. Surprisingly, however, the B. malayi proteins were not capable of rescuing a C. elegans α subunit mutant, whereas the human enzymes could. In contrast, the B. malayi PDI did functionally complement the lethal phenotype of a C. elegans β subunit mutant. Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non-reducible covalent link, present only in the parasite. We therefore demonstrate that C-P4H activity is essential for development of B. malayi and uncover a novel parasite-specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control. PMID:23223450

  10. Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Eren, Emre; Spata, Tyler; Tadres, Malak; Hayes,, Don; Black, Sylvester M.

    2015-01-01

    The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed lung transplantation in humans to become more readily available by enabling the ability to assess organs and expand the donor pool. As this technology expands and improves, the ability to potentially evaluate and improve the quality of substandard lungs prior to transplant is a critical need. In order to more rigorously evaluate these approaches, a reproducible animal model needs to be established that would allow for testing of improved techniques and management of the donated lungs as well as to the lung-transplant recipient. In addition, an EVLP animal model of associated pathologies, e.g., ventilation induced lung injury (VILI), would provide a novel method to evaluate treatments for these pathologies. Here, we describe the development of a rat EVLP lung program and refinements to this method that allow for a reproducible model for future expansion. We also describe the application of this EVLP system to model VILI in rat lungs. The goal is to provide the research community with key information and “pearls of wisdom”/techniques that arose from trial and error and are critical to establishing an EVLP system that is robust and reproducible. PMID:25741794

  11. Microsatellite markers for the human nematode parasite Ascaris lumbricoides: development and assessment of utility.

    PubMed

    Criscione, Charles D; Anderson, Joel D; Raby, Kyle; Sudimack, Dan; Subedi, Janardan; Rai, Dev R; Upadhayay, Ram P; Jha, Bharat; Williams-Blangero, Sarah; Anderson, Timothy J C

    2007-06-01

    We describe 35 microsatellite markers from the human parasitic nematode Ascaris lumbricoides. We found 7 sex-linked markers and demonstrate that 26 autosomal loci can be scored reliably. These markers have high genetic variability and provide the tools to address multiple questions concerning the epidemiology, fine-scale genetic structure, host specificity, and mating systems of this parasite.

  12. Encystation in parasitic protozoa.

    PubMed

    Eichinger, D

    2001-08-01

    Giardia and Entamoeba parasites encase themselves in a carbohydrate-rich cyst for travel from host to host. Both parasites upregulate their Golgi apparatus during this process, yielding organelles that are now found to be similar to those of higher eukaryotes. In fact, unusual enzymes and structural proteins used for cyst wall synthesis, the complexity of the secretory pathways used to transport materials to the developing cyst walls, as well as unexpected mechanisms of gene regulation and parasite-host and parasite-parasite information exchange, are revealing a high level of sophistication in these organisms that occupy low branch points in the eukaryotic lineage.

  13. Parasite annexins--new molecules with potential for drug and vaccine development.

    PubMed

    Hofmann, Andreas; Osman, Asiah; Leow, Chiuan Yee; Driguez, Patrick; McManus, Donald P; Jones, Malcolm K

    2010-11-01

    In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti-parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms.Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine.

  14. Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

    PubMed

    Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

    2015-12-01

    The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

  15. Local Auxin Biosynthesis Mediated by a YUCCA Flavin Monooxygenase Regulates Haustorium Development in the Parasitic Plant Phtheirospermum japonicum[OPEN

    PubMed Central

    Takebayashi, Yumiko; Kasahara, Hiroyuki; Wafula, Eric; dePamphilis, Claude W.; Namba, Shigetou

    2016-01-01

    Parasitic plants in the Orobanchaceae cause serious agricultural problems worldwide. Parasitic plants develop a multicellular infectious organ called a haustorium after recognition of host-released signals. To understand the molecular events associated with host signal perception and haustorium development, we identified differentially regulated genes expressed during early haustorium development in the facultative parasite Phtheirospermum japonicum using a de novo assembled transcriptome and a customized microarray. Among the genes that were upregulated during early haustorium development, we identified YUC3, which encodes a functional YUCCA (YUC) flavin monooxygenase involved in auxin biosynthesis. YUC3 was specifically expressed in the epidermal cells around the host contact site at an early time point in haustorium formation. The spatio-temporal expression patterns of YUC3 coincided with those of the auxin response marker DR5, suggesting generation of auxin response maxima at the haustorium apex. Roots transformed with YUC3 knockdown constructs formed haustoria less frequently than nontransgenic roots. Moreover, ectopic expression of YUC3 at the root epidermal cells induced the formation of haustorium-like structures in transgenic P. japonicum roots. Our results suggest that expression of the auxin biosynthesis gene YUC3 at the epidermal cells near the contact site plays a pivotal role in haustorium formation in the root parasitic plant P. japonicum. PMID:27385817

  16. Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

    PubMed

    Babayan, Simon A; Read, Andrew F; Lawrence, Rachel A; Bain, Odile; Allen, Judith E

    2010-10-19

    Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

  17. Local Auxin Biosynthesis Mediated by a YUCCA Flavin Monooxygenase Regulates Haustorium Development in the Parasitic Plant Phtheirospermum japonicum.

    PubMed

    Ishida, Juliane K; Wakatake, Takanori; Yoshida, Satoko; Takebayashi, Yumiko; Kasahara, Hiroyuki; Wafula, Eric; dePamphilis, Claude W; Namba, Shigetou; Shirasu, Ken

    2016-08-01

    Parasitic plants in the Orobanchaceae cause serious agricultural problems worldwide. Parasitic plants develop a multicellular infectious organ called a haustorium after recognition of host-released signals. To understand the molecular events associated with host signal perception and haustorium development, we identified differentially regulated genes expressed during early haustorium development in the facultative parasite Phtheirospermum japonicum using a de novo assembled transcriptome and a customized microarray. Among the genes that were upregulated during early haustorium development, we identified YUC3, which encodes a functional YUCCA (YUC) flavin monooxygenase involved in auxin biosynthesis. YUC3 was specifically expressed in the epidermal cells around the host contact site at an early time point in haustorium formation. The spatio-temporal expression patterns of YUC3 coincided with those of the auxin response marker DR5, suggesting generation of auxin response maxima at the haustorium apex. Roots transformed with YUC3 knockdown constructs formed haustoria less frequently than nontransgenic roots. Moreover, ectopic expression of YUC3 at the root epidermal cells induced the formation of haustorium-like structures in transgenic P. japonicum roots. Our results suggest that expression of the auxin biosynthesis gene YUC3 at the epidermal cells near the contact site plays a pivotal role in haustorium formation in the root parasitic plant P. japonicum.

  18. Gastrointestinal parasite infestation.

    PubMed

    Abd El Bagi, Mohamed E; Sammak, Bassam M; Mohamed, Abdulrahman E; Al Karawi, Mohamed A; Al Shahed, Mona; Al Thagafi, Mohamed A

    2004-03-01

    Twenty-five percent of the world's population could be suffering parasitic infestation. Highest prevalence is in underdeveloped agricultural and rural areas in the tropical and subtropical regions. In some areas incidence may reach 90% of the population. In contrast, some major economic projects intended to promote local development have, paradoxically, caused parasitic proliferation, e.g. bilharziasis in Egypt and Sudan and Chagas disease in Brazil. The commonest cosmopolitan gastrointestinal parasite is Entamoeba histolytica. Some intestinal parasite are endemic in temperate climates, e.g. Entrobius vermicularis. The AIDS epidemic has increased the prevalence and severity of parasitic disease, particularly Strongyloides stercolaris. Tropical parasites are seen in Western people who travel to tropical countries. Radiology has acquired a major role in diagnosis and management of gastrointestinal parasite infestations and their complications.

  19. Rates of development in male and female Wood Frogs and patterns of parasitism by lung nematodes.

    PubMed

    Dare, O K; Forbes, M R

    2008-03-01

    Researchers are becoming interested in testing whether investment in growth and/or development trades off against investment in parasite defence. We tested this idea by examining relations between development of Wood Frogs (Rana sylvatica) and susceptibility to lung nematodes (Rhabdias ranae). Male and female frogs reared in outdoor mesocosms were the same length and mass at metamorphosis. However, males metamorphosed sooner than females. Lung nematodes were no more likely to penetrate male versus female metamorphs following controlled exposures, but males had higher intensities of adult female worms and the largest worms per host were, on average, of larger size in male metamorphs. Males that took longer to metamorphose carried higher numbers of worms in their lungs than males that metamorphosed early. In comparison, females that developed faster harboured more worms in their lungs than females that took longer to reach metamorphosis. Our results suggest that variation in susceptibility to lung nematodes is influenced by host sex and possibly also by sex-specific relations with developmental rate. Further, male hosts might prove to be a more important source of infective stages of worms than female hosts.

  20. Expression profile of heat shock response factors during hookworm larval activation and parasitic development.

    PubMed

    Gelmedin, Verena; Delaney, Angela; Jennelle, Lucas; Hawdon, John M

    2015-07-01

    When organisms are exposed to an increase in temperature, they undergo a heat shock response (HSR) regulated by the transcription factor heat shock factor 1 (HSF-1). The heat shock response includes the rapid changes in gene expression initiated by binding of HSF-1 to response elements in the promoters of heat shock genes. Heat shock proteins function as molecular chaperones to protect proteins during periods of elevated temperature and other stress. During infection, hookworm infective third stage larvae (L3) undergo a temperature shift from ambient to host temperature. This increased temperature is required for the resumption of feeding and activation of L3, but whether this increase initiates a heat shock response is unknown. To investigate the role of the heat shock in hookworm L3 activation and parasitic development, we identified and characterized the expression profile of several components of the heat shock response in the hookworm Ancylostoma caninum. We cloned DNAs encoding an hsp70 family member (Aca-hsp-1) and an hsp90 family member (Aca-daf-21). Exposure to a heat shock of 42°C for one hour caused significant up-regulation of both genes, which slowly returned to near baseline levels following one hour attenuation at 22°C. Neither gene was up-regulated in response to host temperature (37°C). Conversely, levels of hsf-1 remained unchanged during heat shock, but increased in response to incubation at 37°C. During activation, both hsp-1 and daf-21 are down regulated early, although daf-21 levels increase significantly in non-activated control larvae after 12h, and slightly in activated larvae by 24h incubation. The heat shock response modulators celastrol and KNK437 were tested for their effects on gene expression during heat shock and activation. Pre-incubation with celastrol, an HSP90 inhibitor that promotes heat shock gene expression, slightly up-regulated expression of both hsp-1 and daf-21 during heat shock. KNK437, an inhibitor of heat shock

  1. Nondestructive imaging of plant-parasitic nematode development and host response to nematode pathogenesis.

    PubMed

    Dinh, Phuong T Y; Knoblauch, Michael; Elling, Axel A

    2014-05-01

    The secluded lifestyle of endoparasitic plant nematodes hampers progress toward a comprehensive understanding of plant-nematode interactions. A novel technique that enables nondestructive, long-term observations of a wide range of live nematodes in planta is presented here. As proof of principle, Pratylenchus penetrans, Heterodera schachtii, and Meloidogyne chitwoodi were labeled fluorescently with PKH26 and used to infect Arabidopsis thaliana grown in microscopy rhizosphere chambers. Nematode behavior, development, and morphology were observed for the full duration of each parasite's life cycle by confocal microscopy for up to 27 days after inoculation. PKH26 accumulated in intestinal lipid droplets and had no negative effect on nematode infectivity. This technique enabled visualization of Meloidogyne gall formation, nematode oogenesis, and nematode morphological features, such as the metacorpus, vulva, spicules, and cuticle. Additionally, microscopy rhizosphere chambers were used to characterize plant organelle dynamics during M. chitwoodi infection. Peroxisome abundance strongly increased in early giant cells but showed a marked decrease at later stages of feeding site development, which suggests a modulation of plant peroxisomes by root-knot nematodes during the infection process. Taken together, this technique facilitates studies aimed at deciphering plant-nematode interactions at the cellular and subcellular level and enables unprecedented insights into nematode behavior in planta.

  2. From commensalism to parasitism in Carapidae (Ophidiiformes): heterochronic modes of development?

    PubMed

    Parmentier, Eric; Lanterbecq, Déborah; Eeckhaut, Igor

    2016-01-01

    Phenotypic variations allow a lineage to move into new regions of the adaptive landscape. The purpose of this study is to analyse the life history of the pearlfishes (Carapinae) in a phylogenetic framework and particularly to highlight the evolution of parasite and commensal ways of life. Furthermore, we investigate the skull anatomy of parasites and commensals and discuss the developmental process that would explain the passage from one form to the other. The genus Carapus forms a paraphyletic grouping in contrast to the genus Encheliophis, which forms a monophyletic cluster. The combination of phylogenetic, morphologic and ontogenetic data clearly indicates that parasitic species derive from commensal species and do not constitute an iterative evolution from free-living forms. Although the head morphology of Carapus species differs completely from Encheliophis, C. homei is the sister group of the parasites. Interestingly, morphological characteristics allowing the establishment of the relation between Carapus homei and Encheliophis spp. concern the sound-producing mechanism, which can explain the diversification of the taxon but not the acquisition of the parasite morphotype. Carapus homei already has the sound-producing mechanism typically found in the parasite form but still has a commensal way of life and the corresponding head structure. Moreover, comparisons between the larval and adult Carapini highlight that the adult morphotype "Encheliophis" is obtained by going beyond the adult stage reached by Carapus. The entrance into the new adaptive landscape could have been realised by at least two processes: paedomorphosis and allometric repatterning.

  3. From commensalism to parasitism in Carapidae (Ophidiiformes): heterochronic modes of development?

    PubMed Central

    Lanterbecq, Déborah; Eeckhaut, Igor

    2016-01-01

    Phenotypic variations allow a lineage to move into new regions of the adaptive landscape. The purpose of this study is to analyse the life history of the pearlfishes (Carapinae) in a phylogenetic framework and particularly to highlight the evolution of parasite and commensal ways of life. Furthermore, we investigate the skull anatomy of parasites and commensals and discuss the developmental process that would explain the passage from one form to the other. The genus Carapus forms a paraphyletic grouping in contrast to the genus Encheliophis, which forms a monophyletic cluster. The combination of phylogenetic, morphologic and ontogenetic data clearly indicates that parasitic species derive from commensal species and do not constitute an iterative evolution from free-living forms. Although the head morphology of Carapus species differs completely from Encheliophis, C. homei is the sister group of the parasites. Interestingly, morphological characteristics allowing the establishment of the relation between Carapus homei and Encheliophis spp. concern the sound-producing mechanism, which can explain the diversification of the taxon but not the acquisition of the parasite morphotype. Carapus homei already has the sound-producing mechanism typically found in the parasite form but still has a commensal way of life and the corresponding head structure. Moreover, comparisons between the larval and adult Carapini highlight that the adult morphotype “Encheliophis” is obtained by going beyond the adult stage reached by Carapus. The entrance into the new adaptive landscape could have been realised by at least two processes: paedomorphosis and allometric repatterning. PMID:26989623

  4. Cultivation of parasites.

    PubMed

    Ahmed, Nishat Hussain

    2014-07-01

    Parasite cultivation techniques constitute a substantial segment of present-day study of parasites, especially of protozoa. Success in establishing in vitro and in vivo culture of parasites not only allows their physiology, behavior and metabolism to be studied dynamically, but also allows the nature of the antigenic molecules in the excretory and secretory products to be vigorously pursued and analyzed. The complex life-cycles of various parasites having different stages and host species requirements, particularly in the case of parasitic helminths, often make parasite cultivation an uphill assignment. Culturing of parasites depends on the combined expertise of all types of microbiological cultures. Different parasites require different cultivation conditions such as nutrients, temperature and even incubation conditions. Cultivation is an important method for diagnosis of many clinically important parasites, for example, Entamoeba histolytica, Trichomonas vaginalis, Leishmania spp., Strongyloides stercoralis and free-living amoebae. Many commercial systems like InPouch TV for T. vaginalis, microaerophilous stationary phase culture for Babesia bovis and Harada-Mori culture technique for larval-stage nematodes have been developed for the rapid diagnosis of the parasitic infections. Cultivation also has immense utility in the production of vaccines, testing vaccine efficacy, and antigen - production for obtaining serological reagents, detection of drug-resistance, screening of potential therapeutic agents and conducting epidemiological studies. Though in vitro cultivation techniques are used more often compared with in vivo techniques, the in vivo techniques are sometimes used for diagnosing some parasitic infections such as trypanosomiasis and toxoplasmosis. Parasite cultivation continues to be a challenging diagnostic option. This review provides an overview of intricacies of parasitic culture and update on popular methods used for cultivating parasites.

  5. Development of a gel formulation of formic acid for control of parasitic mites of honey bees.

    PubMed

    Kochansky, J; Shimanuki, H

    1999-09-01

    Formic acid has been used in various countries for the control of parasitic mites of honey bees (Apis mellifera), particularly the Varroa mite (Varroa jacobsoni) and the tracheal mite (Acarapis woodi). Its corrosivity and consequent fear of liability have precluded commercial interest in the United States, and its rapid vaporization requires frequent reapplication. We have developed a gel formulation of formic acid which provides controlled release over 2-3 weeks and improves the convenience and safety of handling of formic acid. The strong acidity of formic acid restricts the choice of gelling agents; vegetable gellants such as agar are destroyed, and bentonite clay derivatives do not gel, even with high-shear mixing. Polyacrylamides lead to viscous liquids lacking thixotropic properties. High-molecular-weight poly(acrylic acids) and fumed silicas provided gels with suitable physical characteristics. The poly(acrylic acid) gels were difficult to mix and gave slower and nonlinear release behavior, while the fumed silica gels were easy to prepare and linear in formic acid vaporization.

  6. Malaria Parasites: The Great Escape

    PubMed Central

    Rénia, Laurent; Goh, Yun Shan

    2016-01-01

    Parasites of the genus Plasmodium have a complex life cycle. They alternate between their final mosquito host and their intermediate hosts. The parasite can be either extra- or intracellular, depending on the stage of development. By modifying their shape, motility, and metabolic requirements, the parasite adapts to the different environments in their different hosts. The parasite has evolved to escape the multiple immune mechanisms in the host that try to block parasite development at the different stages of their development. In this article, we describe the mechanisms reported thus far that allow the Plasmodium parasite to evade innate and adaptive immune responses. PMID:27872623

  7. Interacting parasites

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2010-01-01

    Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

  8. [Effects of temperature on the growth and development of Aglossa dimidiata parasitized on Litsea coreana].

    PubMed

    Shang, Xiao-Li; Yang, Mao-Fa; Huang, Li; Gou, Guang-Qian

    2012-11-01

    In order to reveal the effects of temperature on the growth and development of Aglossa dimidiata parasitized on Litsea coreana, a laboratory experiment was conducted to study the mean development duration, development rate, and survival rate of A. dimidiata at its different growth stages at 31 degrees C, 28 degrees C, 25 degrees C, 22 degrees C, and 19 degrees C, with the development threshold temperature and effective accumulated temperature for different growth stages calculated. Temperature had significant effects on the developmental duration. Except that the development duration of egg was shortened with increasing temperature, the development durations of larva, pupa, and immature A. dimidiata were the shortest at 25 degrees C, being 249.53 +/- 23.83, 12.94 +/- 1.27, and 273.00 +/- 24.19 days, respectively. There existed significant relationships between the development rates of A. dimidiata at its different growth stages and temperature, with positive linear relationship at egg stage, and quadratic relationship at larva, pupa, and immature stages. Temperature also had significant effects on the survival rate of A. dimidiata. The survival rates of A. dimidiata at its different growth stages were all the highest at 25 degrees C, being 94.0%, 73.8%, 91.3%, and 63.4% for the egg, larva, pupa, and immature A. dimidiata, respectively, followed by at 22 degrees C and 19 degrees C, and the lowest at 31 degrees C. No larva and pupa could survive at 31 degrees C, suggesting that A. dimidiata was not resistant to high temperature. The development threshold temperature for egg, larva, pupa, and immature A. dimidiata was 13.21 degrees C, 17.12 degrees C, 14.76 degrees C, and 16.47 degrees C, and the effective accumulated temperature was 117.94, 870.88, 149.70, and 1442.75 day-degree, respectively. The results coincided with the fact that the A. dimidiata reproduced 2 or 3 generations a year in Xifeng area of Guizhou, Southwest China.

  9. Systematic errors in temperature estimates from MODIS data covering the western Palearctic and their impact on a parasite development model.

    PubMed

    Alonso-Carné, Jorge; García-Martín, Alberto; Estrada-Peña, Agustin

    2013-11-01

    The modelling of habitat suitability for parasites is a growing area of research due to its association with climate change and ensuing shifts in the distribution of infectious diseases. Such models depend on remote sensing data and require accurate, high-resolution temperature measurements. The temperature is critical for accurate estimation of development rates and potential habitat ranges for a given parasite. The MODIS sensors aboard the Aqua and Terra satellites provide high-resolution temperature data for remote sensing applications. This paper describes comparative analysis of MODIS-derived temperatures relative to ground records of surface temperature in the western Palaearctic. The results show that MODIS overestimated maximum temperature values and underestimated minimum temperatures by up to 5-6 °C. The combined use of both Aqua and Terra datasets provided the most accurate temperature estimates around latitude 35-44° N, with an overestimation during spring-summer months and an underestimation in autumn-winter. Errors in temperature estimation were associated with specific ecological regions within the target area as well as technical limitations in the temporal and orbital coverage of the satellites (e.g. sensor limitations and satellite transit times). We estimated error propagation of temperature uncertainties in parasite habitat suitability models by comparing outcomes of published models. Error estimates reached 36% of annual respective measurements depending on the model used. Our analysis demonstrates the importance of adequate image processing and points out the limitations of MODIS temperature data as inputs into predictive models concerning parasite lifecycles.

  10. Arrested development of the myxozoan parasite, Myxobolus cerebralis, in certain populations of mitochondrial 16S lineage III Tubifex tubifex

    USGS Publications Warehouse

    Baxa, D.V.; Kelley, G.O.; Mukkatira, K.S.; Beauchamp, K.A.; Rasmussen, C.; Hedrick, R.P.

    2008-01-01

    Laboratory populations of Tubifex tubifex from mitochondrial (mt)16S ribosomal DNA (rDNA) lineage III were generated from single cocoons of adult worms releasing the triactinomyxon stages (TAMs) of the myxozoan parasite, Myxobolus cerebralis. Subsequent worm populations from these cocoons, referred to as clonal lines, were tested for susceptibility to infection with the myxospore stages of M. cerebralis. Development and release of TAMs occurred in five clonal lines, while four clonal lines showed immature parasitic forms that were not expelled from the worm (non-TAM producers). Oligochaetes from TAM- and non-TAM-producing clonal lines were confirmed as lineage III based on mt16S rDNA and internal transcribed spacer region 1 (ITS1) sequences, but these genes did not differentiate these phenotypes. In contrast, random amplified polymorphic DNA analyses of genomic DNA demonstrated unique banding patterns that distinguished the phenotypes. Cohabitation of parasite-exposed TAM- and non-TAM-producing phenotypes showed an overall decrease in expected TAM production compared to the same exposure dose of the TAM-producing phenotype without cohabitation. These studies suggest that differences in susceptibility to parasite infection can occur in genetically similar T. tubifex populations, and their coexistence may affect overall M. cerebralis production, a factor that may influence the severity of whirling disease in wild trout populations. ?? 2007 Springer-Verlag.

  11. Interactions of environmental stressors impact survival and development of parasitized larval amphibians.

    PubMed

    Koprivnikar, J

    2010-12-01

    Infected hosts are exposed to many environmental stressors that must be taken into account in order to determine the importance of disease, as various combinations can interact in unpredictable ways. Here, northern leopard frog (Rana pipiens) tadpoles, a species in decline, were exposed to stressors singly or in combination. Stressors included infection by Echinostoma trivolvis (a trematode parasite), exposure to predator chemical cues (larval dragonflies), and exposure to varying concentrations of the herbicide atrazine. Parasitism decreased survival only in combination with exposure to 3 microg/L atrazine, with a negative interaction observed for mass as well. Similarly, a negative interaction of parasitism and predation on survival occurred. However, atrazine exposure alone negatively affected the survival, mass, and developmental stage of tadpoles. These results indicate that certain stressor combinations are particularly deleterious for young parasitized tadpoles. Notably, very common low-intensity parasite infection can be particularly harmful in certain situations. Such negative impacts on larval amphibians in certain scenarios may contribute to ongoing amphibian population declines, emphasizing that the combination of environmental stressors must be considered when evaluating the general role of disease in species extinctions.

  12. Technetium myocardial perfusion agents: an introduction

    SciTech Connect

    English, R.J.; Kozlowski, J.; Tumeh, S.S.; Holman, B.L.

    1987-09-01

    This is the third in a series of four Continuing Education articles on developing radiopharmaceuticals. After reading this article, the reader should be able to: 1) understand the basic concepts of myocardial perfusion imaging; and 2) discuss the advantages of the technetium myocardial perfusion complexes over thallium-201.

  13. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  14. Oestrogen-induced angiogenesis and implantation contribute to the development of parasitic myomas after laparoscopic morcellation.

    PubMed

    Huang, Ben-Shian; Yang, Muh-Hwa; Wang, Peng-Hui; Li, Hsin-Yang; Chou, Teh-Ying; Chen, Yi-Jen

    2016-10-06

    Iatrogenic parasitic myomas (PMs), caused by intra-corporeal power morcellation during laparoscopy is gradually increasing. However, the pathogenesis and medical treatment of PMs remain largely unelucidated. Laparoscopically-induced PM xenografted mouse model was conducted by xenografting human uterine myoma fragments into the abdominal cavity of SCID mice and hormonal manipulation was performed using this mouse model to demonstrate the role of oestrogen in the development of implanted PMs. Immunohistochemistry of oestrogen receptor α (ERα), progesterone receptor (PR), vimentin, vascular endothelial growth factor (VEGF), microvessel density (MVD) and Ki-67 index was performed and compared. In the patient with PMs, ERα, PR, angiogenesis and proliferative property expression were upregulated in PM lesions compared to uterine myomas. In the laparoscopically-induced PM mouse model, implanted myomas had more steroid receptor expressions, angiogenesis and proliferative property compared with pre-xenografted or non-implanted myoma. Depletion of oestrogen in the ovariectomized (OVX) mice decreased laparoscopically-induced PM implantations. In comparison, the implantations of PMs were increased with additional E2 supplement. Hormonal manipulation in the PM mouse model, including AI, GnRHa and SERM groups, were compared and AI significantly decreased the implantations, steroid receptor, angiogenesis, cell density, and proliferative index of PMs compared with control group. Furthermore, GnRHa significantly decreased VEGF and MVD expressions compared with control group. These data highlight the crucial role of oestrogen in the development of laparoscopically-induced PMs and suggest that hormone manipulation may be a potential therapeutic agent. This protocol was approved by the Human and Animal Institutional Review Board of Taipei Veterans General Hospital ( VGHIRB No 2014-10-002C on Nov. 17(th), 2014; IACUC 2014-119 on Aug. 22(nd), 2014).

  15. Interaction between Orobanche crenata and its Host Legumes: Unsuccessful Haustorial Penetration and Necrosis of the Developing Parasite

    PubMed Central

    PÉREZ-DE-LUQUE, A.; RUBIALES, D.; CUBERO, J. I.; PRESS, M. C.; SCHOLES, J.; YONEYAMA, K.; TAKEUCHI, Y.; PLAKHINE, D.; JOEL, D. M.

    2005-01-01

    • Background and Aims Orobanche species represent major constraints to crop production in many parts of the world as they reduce yield and alter root/shoot allometry. Although much is known about the histology and effect of Orobanche spp. on susceptible hosts, less is known about the basis of host resistance to these parasites. In this work, histological aspects related to the resistance of some legumes to Orobanche crenata have been investigated in order to determine which types of resistance responses are involved in the unsuccessful penetration of O. crenata. • Methods Samples of resistance reactions against O. crenata on different genotypes of resistant legumes were collected. The samples were fixed, sectioned and stained using different procedures. Sections were observed using a transmission light microscope and by epi-fluorescence. • Key Results Lignification of endodermal and pericycle host cells seems to prevent parasite intrusion into the root vascular cylinder at early infection stages. But in other cases, established tubercles became necrotic and died. Contrary to some previous studies, it was found that darkening at the infection site in these latter cases does not correspond to death of host tissues, but to the secretion of substances that fill the apoplast in the host–parasite interface and in much of the infected host tissues. The secretions block neighbouring host vessels. This may interfere with the nutrient flux between host and parasite, and may lead to necrosis and death of the developing parasite. • Conclusions The unsuccessful penetration of O. crenata seedlings into legume roots cannot be attributed to cell death in the host. It seems to be associated with lignification of host endodermis and pericycle cells at the penetration site. The accumulation of secretions at the infection site, may lead to the activation of xylem occlusion, another defence mechanism, which may cause further necrosis of established tubercles. PMID:15749751

  16. Development of novel valerolactam-benzimidazole hybrids anthelmintic derivatives: Diffusion and biotransformation studies in helminth parasites.

    PubMed

    Munguía, Beatriz; Michelena, Mauricio; Melian, Elisa; Saldaña, Jenny; Ures, Ximena; Manta, Eduardo; Domínguez, Laura

    2015-06-01

    In the search for new anthelmintics able to overcome the resistance problem against all available drugs in livestock, the synthesis of novel valerolactam-benzimidazole hybrid compounds was reported. This allowed us to obtain these in vitro and in vivo bioactive compounds using Nippostrongylus brasiliensis rat model by integrating physiology-based assays and ex vivo diffusion studies. In order to further study those novel hybrid molecules, Haemonchus contortus (a sheep gastrointestinal nematode of interest) and Mesocestoides vogae tetrathyridia (a useful system to study the efficacy of anthelmintic drugs against cestoda) were used as parasite models to compare the ex vivo patterns of diffusion and biotransformation of benzimidazoles and their valerolactam-benzimidazole hybrid derivatives. On average, a nine-fold higher intraparasitic concentration of compounds was found in M. vogae compared with H.contortus, with similarities regarding the order of entry of compounds, highlighting febendazole (FEB) and its hybrid compound 10, while valerolactam compound 2 practically did not penetrate the parasites. Interestingly, sulphoxidation drug metabolism was observed and measured, revealing percentages of oxidation of 8.2% and 14.5% for albendazole (ABZ) and febendazole respectively in M. vogae, while this effect was more relevant in H. contortus parasite. More importantly, significant differences were observed between anthelmintic-susceptible adult parasites (Hc S) and those from sheep farms (Hc U). In fact, the percentages of oxidation of FEB and the hybrid compound 8 were higher in Hc U (25.5%, 54.1%, respectively) than in Hc S (8.8%, 38.2%). Interestingly, sulphoxidation of hybrid compound 10 was neither observed in M. vogae nor in H. contortus parasites, suggesting that increased drug metabolism (oxidation reactions) could not be used by these parasites as a defense mechanism against this novel drug. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Nuclear DNA replication and repair in parasites of the genus Leishmania: Exploiting differences to develop innovative therapeutic approaches.

    PubMed

    Uzcanga, Graciela; Lara, Eliana; Gutiérrez, Fernanda; Beaty, Doyle; Beske, Timo; Teran, Rommy; Navarro, Juan-Carlos; Pasero, Philippe; Benítez, Washington; Poveda, Ana

    2017-03-01

    Leishmaniasis is a common tropical disease that affects mainly poor people in underdeveloped and developing countries. This largely neglected infection is caused by Leishmania spp, a parasite from the Trypanosomatidae family. This parasitic disease has different clinical manifestations, ranging from localized cutaneous to more harmful visceral forms. The main limitations of the current treatments are their high cost, toxicity, lack of specificity, and long duration. Efforts to improve treatments are necessary to deal with this infectious disease. Many approved drugs to combat diseases as diverse as cancer, bacterial, or viral infections take advantage of specific features of the causing agent or of the disease. Recent evidence indicates that the specific characteristics of the Trypanosomatidae replication and repair machineries could be used as possible targets for the development of new treatments. Here, we review in detail the molecular mechanisms of DNA replication and repair regulation in trypanosomatids of the genus Leishmania and the drugs that could be useful against this disease.

  18. History and development of research on wildlife parasites in southern Africa, with emphasis on terrestrial mammals, especially ungulates

    PubMed Central

    Junker, Kerstin; Horak, Ivan G.; Penzhorn, Banie

    2014-01-01

    The history of wildlife parasitology in South Africa, and to some extent southern Africa, is reviewed, giving a brief overview of the early years and following its development from the founding of the Onderstepoort Veterinary Institute in 1908 until the turn of the century. An emphasis is placed on game species. The main findings on protozoan parasites, including those of carnivores, are presented, starting in the 1890s and leading up to the first decade of the 21st century. Important developments with regard to the studies of arthropod and helminth parasites took place during a period of three decades, starting from the 1970s. Because of the sheer volume of work done by parasitologists during this time, this particular part of the overview concentrates on South African authors or authors working in South Africa at the time, and is limited to hosts that are members of the order Perissodactyla and the superorder Cetartiodactyla. PMID:25830101

  19. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

    PubMed

    Yoshida, Shigeto; Shimada, Yohei; Kondoh, Daisuke; Kouzuma, Yoshiaki; Ghosh, Anil K; Jacobs-Lorena, Marcelo; Sinden, Robert E

    2007-12-01

    The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions.

  20. The Cytoplasmic Prolyl-tRNA Synthetase of the Malaria Parasite is a Dual-Stage Target for Drug Development

    PubMed Central

    Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.; Ribacke, Ulf; Lukens, Amanda K.; Santos, Sofia A.; Patel, Vishal; Clish, Clary B.; Sullivan, William J.; Zhou, Huihao; Bopp, Selina E.; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M.; Keller, Tracy L.; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F.; Mazitschek, Ralph

    2015-01-01

    The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials. PMID:25995223

  1. Purine import into malaria parasites as a target for antimalarial drug development.

    PubMed

    Frame, I J; Deniskin, Roman; Arora, Avish; Akabas, Myles H

    2015-04-01

    Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1-4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is expressed in all parasite stages. PfENT1 knockout parasites are not viable in culture at purine concentrations found in human blood (<10 μM). Thus, PfENT1 is a potential target for novel antimalarial drugs, but no PfENT1 inhibitors have been identified to test the hypothesis. Identifying inhibitors of PfENT1 is an essential step to validate PfENT1 as a potential antimalarial drug target.

  2. Predictability of helminth parasite host range using information on geography, host traits and parasite community structure.

    PubMed

    Dallas, Tad; Park, Andrew W; Drake, John M

    2017-02-01

    Host-parasite associations are complex interactions dependent on aspects of hosts (e.g. traits, phylogeny or coevolutionary history), parasites (e.g. traits and parasite interactions) and geography (e.g. latitude). Predicting the permissive host set or the subset of the host community that a parasite can infect is a central goal of parasite ecology. Here we develop models that accurately predict the permissive host set of 562 helminth parasites in five different parasite taxonomic groups. We developed predictive models using host traits, host taxonomy, geographic covariates, and parasite community composition, finding that models trained on parasite community variables were more accurate than any other covariate group, even though parasite community covariates only captured a quarter of the variance in parasite community composition. This suggests that it is possible to predict the permissive host set for a given parasite, and that parasite community structure is an important predictor, potentially because parasite communities are interacting non-random assemblages.

  3. Accelerated Dual-contrast First-pass Perfusion MRI of the Mouse Heart: Development and Application to Diet-induced Obese Mice

    PubMed Central

    Naresh, Nivedita K.; Chen, Xiao; Roy, Rene J.; Antkowiak, Patrick F.; Annex, Brian H.; Epstein, Frederick H.

    2014-01-01

    Background Gene-modified mice may be used to elucidate molecular mechanisms underlying abnormal myocardial blood flow (MBF). We sought to develop a quantitative myocardial perfusion imaging technique for mice and to test the hypothesis that myocardial perfusion reserve (MPR) is reduced in a mouse model of diet-induced obesity (DIO). Methods A dual-contrast saturation-recovery sequence with ky-t undersampling and a motion-compensated compressed sensing reconstruction algorithm was developed for first-pass MRI on a small-bore 7T system. Control mice were imaged at rest and with the vasodilators ATL313 and Regadenoson (n=6 each). In addition, we imaged mice fed a high-fat diet (HFD) for 24 weeks. Results In control mice, MBF was 5.7±0.8 ml/g/min at rest and it increased to 11.8±0.6 ml/g/min with ATL313 and to 10.4±0.3 ml/g/min with Regadenoson. In HFD mice we detected normal resting MBF (5.6±0.4 vs. 5.0±0.3 on control diet), low MBF at stress (7.7±0.4 vs. 10.4±0.3 on control diet, p<0.05), and reduced MPR (1.4±0.2 vs. 2.0±0.3 on control diet, p<0.05). Conclusions Accelerated dual-contrast first-pass MRI with motion-compensated compressed sensing provides spatiotemporal resolution suitable for measuring MBF in free-breathing mice, and detected reduced MPR in DIO mice. These techniques may be used to study molecular mechanisms that underlie abnormal myocardial perfusion. PMID:24760707

  4. Plasmodium berghei Δp52&p36 parasites develop independent of a parasitophorous vacuole membrane in Huh-7 liver cells.

    PubMed

    Ploemen, Ivo H J; Croes, Huib J; van Gemert, Geert-Jan J; Wijers-Rouw, Mietske; Hermsen, Cornelus C; Sauerwein, Robert W

    2012-01-01

    The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Δp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM). However, a small proportion of P. berghei Δp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Δp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Δp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Δp52&p36 parasites were able to fully mature and produced infectious merozoites. These Δp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Δp52&p36 liver stages were infectious for C57BL/6 mice.

  5. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  6. Evolutionarily conserved CLE peptide signaling in plant development, symbiosis, and parasitism.

    PubMed

    Miyawaki, Kaori; Tabata, Ryo; Sawa, Shinichiro

    2013-10-01

    Small polypeptides are widely used as signaling molecules in cell-to-cell communication in animals and plants. The CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) gene family is composed of numerous genes that contain conserved CLE domains in various plant species and plant-parasitic nematodes. Here, we review recent progress in our understanding of CLE signaling during stem cell maintenance in Arabidopsis and grasses. We also summarize the roles of CLE signaling in the legume-Rhizobium symbiosis and infection by plant-parasitic nematodes. CLE signaling is important for diverse aspects of cell-to-cell signaling and long-distance communication, which are critical for survival, and the basic components of the CLE signaling pathway are evolutionarily conserved in both plants and animals.

  7. Plasmodium falciparum 19-kilodalton merozoite surface protein 1 (MSP1)-specific antibodies that interfere with parasite growth in vitro can inhibit MSP1 processing, merozoite invasion, and intracellular parasite development.

    PubMed

    Moss, David K; Remarque, Edmond J; Faber, Bart W; Cavanagh, David R; Arnot, David E; Thomas, Alan W; Holder, Anthony A

    2012-03-01

    Merozoite surface protein 1 (MSP1) is a target for malaria vaccine development. Antibodies to the 19-kDa carboxy-terminal region referred to as MSP1(19) inhibit erythrocyte invasion and parasite growth, with some MSP1-specific antibodies shown to inhibit the proteolytic processing of MSP1 that occurs at invasion. We investigated a series of antibodies purified from rabbits immunized with MSP1(19) and AMA1 recombinant proteins for their ability to inhibit parasite growth, initially looking at MSP1 processing. Although significant inhibition of processing was mediated by several of the antibody samples, there was no clear relationship with overall growth inhibition by the same antibodies. However, no antibody samples inhibited processing but not invasion, suggesting that inhibition of MSP1 processing contributes to but is not the only mechanism of antibody-mediated inhibition of invasion and growth. Examining other mechanisms by which MSP1-specific antibodies inhibit parasite growth, we show that MSP1(19)-specific antibodies are taken up into invaded erythrocytes, where they persist for significant periods and result in delayed intracellular parasite development. This delay may result from antibody interference with coalescence of MSP1(19)-containing vesicles with the food vacuole. Antibodies raised against a modified recombinant MSP1(19) sequence were more efficient at delaying intracellular growth than those to the wild-type protein. We propose that antibodies specific for MSP1(19) can mediate inhibition of parasite growth by at least three mechanisms: inhibition of MSP1 processing, direct inhibition of invasion, and inhibition of parasite development following invasion. The balance between mechanisms may be modulated by modifying the immunogen used to induce the antibodies.

  8. Development of a dynamic model for real-time determination of membrane-bound acetylcholinesterase activity upon perfusion with inhibitors and reactivators.

    PubMed

    Eckert, Saskia; Eyer, Peter; Mückter, Harald; Worek, Franz

    2006-07-28

    Quantitative predictions of the course of acetylcholinesterase (AChE) activity, following interference of inhibitors and reactivators, are usually obscured by the time-dependent changes of all reaction partners. To mimic these dynamics we developed an in vitro model. Immobilized human erythrocyte ghosts in a bioreactor were continuously perfused while AChE activity was monitored by a modified Ellman method. The perfusion system consisted of two HPLC pumps with integrated quaternary low-pressure gradient formers that were programmed by a computer using commercial HPLC software. The combined eluates passed a particle filter (Millex-GS, 0.22 microm) containing a thin layer of erythrocytes that was immersed in a temperature-controlled water bath. The effluent passed a flow cell in a UV-vis detector, the signal of which was digitized, written to disc and calculated with curve fitting programs. AChE activity decreased by 3.4% within 2.5 h. The day-to-day variation of the freshly prepared bioreactor using the same enzyme source was +/-3.3%. Residual activity of 0.2% marked the limit of quantification. Following perfusion with paraoxon, pseudo first-order rate constants of inhibition were established that did not differ from results obtained in conventional assays. The same holds true for reactivation with obidoxime. The set-up presented allows freely programmable time-dependent changes of up to eight solvents to mimic pharmacokinetic profiles without accumulation of products. Due to some hysteresis in the system, reaction half-lives should be >3 min and concentration changes in critical compounds should exceed half-lives of 5 min. Otherwise, the system offers much flexibility and operates with high precision.

  9. Field-cage evaluation of parasitism, development, and overwintering of two recently introduced biological control agents of the emerald ash borer

    USDA-ARS?s Scientific Manuscript database

    Field-cages were used to evaluate the abilities of Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) and Spathius agrili Yang (Hymenoptera: Braconidae), biocontrol agents of Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), to parasitize, develop and overwinter following three late-sea...

  10. Experimental ovine toxoplasmosis: influence of the gestational stage on the clinical course, lesion development and parasite distribution.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Regidor-Cerrillo, Javier; Ferre, Ignacio; Fernández, Miguel; Ferreras, M Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Pereira-Bueno, Juana; Katzer, Frank; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2016-03-16

    The relation between gestational age and foetal death risk in ovine toxoplasmosis is already known, but the mechanisms involved are not yet clear. In order to study how the stage of gestation influences these mechanisms, pregnant sheep of the same age and genetic background were orally dosed with 50 oocysts of Toxoplasma gondii (M4 isolate) at days 40 (G1), 90 (G2) and 120 (G3) of gestation. In each group, four animals were culled on the second, third and fourth week post infection (pi) in order to evaluate parasite load and distribution, and lesions in target organs. Ewes from G1 showed a longer period of hyperthermia than the other groups. Abortions occurred in all groups. While in G2 they were more frequent during the acute phase of the disease, in G3 they mainly occurred after day 20 pi. After challenge, parasite and lesions in the placentas and foetuses were detected from day 19 pi in G3 while in G2 or G1 they were only detected at day 26 pi. However, after initial detection at day 19 pi, parasite burden, measured through RT-PCR, in placenta or foetus of G3 did not increase significantly and, at in the third week pi it was lower than that measured in foetal liver or placenta from G1 to G3 respectively. These results show that the period of gestation clearly influences the parasite multiplication and development of lesions in the placenta and foetus and, as a consequence, the clinical course in ovine toxoplasmosis.

  11. Dynamics of the Major Histocompatibility Complex Class I Processing and Presentation Pathway in the Course of Malaria Parasite Development in Human Hepatocytes: Implications for Vaccine Development

    PubMed Central

    Ma, Jinxia; Trop, Stefanie; Baer, Samantha; Rakhmanaliev, Elian; Arany, Zita; Dumoulin, Peter; Zhang, Hao; Romano, Julia; Coppens, Isabelle; Levitsky, Victor; Levitskaya, Jelena

    2013-01-01

    Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert the MHC class I presentation machinery, its functionality in the course of malaria replication in hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of the MHC class I pathway exhibit largely unaltered expression in malaria-infected hepatocytes until very late stages of parasite development. Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells. We further demonstrate that ectopic expression of circumsporozoite protein does not alter expression of critical genes of the MHC class I pathway and its response to pro-inflammatory cytokines. In addition, we identified supra-cellular structures, which arose at late stages of parasite replication, possessed the characteristic morphology of merosomes and exhibited nearly complete loss of surface MHC class I expression. These data have multiple implications for our understanding of natural T-cell immunity against malaria and may promote development of novel, efficient anti-malaria vaccines overcoming immune escape of the parasite in the liver. PMID:24086507

  12. Parasites that cause problems in Malaysia: soil-transmitted helminths and malaria parasites.

    PubMed

    Singh, B; Cox-Singh, J

    2001-12-01

    Malaysia is a developing country with a range of parasitic infections. Indeed, soil-transmitted helminths and malaria parasites continue to have a significant impact on public health in Malaysia. In this article, the prevalence and distribution of these parasites, the problems associated with parasitic infections, the control measures taken to deal with these parasites and implications for the future will be discussed.

  13. Parasitism, emergence, and development of Spalangia endius (Hymenoptera: Pteromalidae) in pupae of different ages of Bactrocera cucurbitae (Diptera: Tephritidae).

    PubMed

    Tang, Liang-De; Ji, Xun-Cong; Han, Yun; Fu, Bu-Li; Liu, Kui

    2015-01-01

    The wasp Spalangia endius Walker (Hymenoptera: Pteromalidae) is a major parasitoid of the pupae of fruit flies, which are a common agricultural pest. An understanding of this intricate host-parasitoid interaction could provide basic information necessary for the sustainable integrated biological control of fruit flies. In this study, we investigated the effect of S. endius on different-aged pupae of the melon fly Bactrocera cucurbitae Coquillett by using choice and nonchoice tests under laboratory conditions. We showed that S. endius females oviposited, and their progeny successfully developed, in different-aged pupae of B. cucurbitae regardless of the method of exposure. There was an oviposition preference for 3-5-d-old pupa. The highest mean percentage parasitism occurred on 4- and 5-d-old hosts, followed by 2- and 3-d-old hosts. The average development time for both males and females was significantly longer in 6-7-d-old hosts than in the younger host stages. Adult females that developed from younger host pupae (2-5-d old) were significantly heavier than those from older host pupae (6-7-d old), and they also lived longer. The sex ratio (proportion of females) of the parasite progeny decreased with an increase in host age. Host mortality also decreased gradually as the pupal age increased. The differences in development time, body weight, and longevity between females and males were significant. These results suggest that S. endius is a good candidate for the biological control of B. cucurbitae.

  14. Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae).

    PubMed

    Suneja, Amita; Gulia, Monika; Gakhar, S K

    2003-02-01

    Rabbits were immunized three times with extracts of Anopheles stephensi midgut. Immunized rabbits showed a high titer of antibodies when characterized by ELISA. We investigated the effect of anti-mosquito midgut antibodies on mosquito fecundity, longevity, mortality, engorgement, and the development of the malaria parasite in mosquitoes. Fecundity was reduced significantly (38%) and similarly hatchability by about 43.5%. There was no statistically significant effect on mortality, longevity, and engorgement. When the mosquito blood meal contained anti-midgut antibodies, fewer oocysts of Plasmodium vivax developed in the mosquito midgut and the proportion of mosquitoes becoming infected was significantly reduced. We also found that the midgut antibodies inhibit the development and/or translocation of the sporozoites. Antisera raised against midgut of A. stephensi recognized eight polypeptides (110, 92, 70, 45, 38, 29, 15, 13 kDa) by Western blotting. Cross-reactive antigens/epitopes present in other tissues of A. stephensi were also examined both by Western blotting and in vivo ELISA. Together, these observations open an avenue for research toward the development of a vector-based malaria parasite transmission blocking vaccine and/or anti-mosquito vaccine.

  15. Development of abamectin loaded plant virus nanoparticles for efficacious plant parasitic nematode control.

    PubMed

    Cao, Jing; Guenther, Richard H; Sit, Tim L; Lommel, Steven A; Opperman, Charles H; Willoughby, Julie A

    2015-05-13

    Plant parasitic nematodes are one of the world's major agricultural pests, causing in excess of $157 billion in worldwide crop damage annually. Abamectin (Abm) is a biological pesticide with a strong activity against a wide variety of plant parasitic nematodes. However, Abm's poor mobility in the soil compromises its nematicide performance because of the limited zone of protection surrounding the growing root system of the plant. In this study, we manipulated Abm's soil physical chemistry by encapsulating Abm within the Red clover necrotic mosaic virus (RCNMV) to produce a plant virus nanoparticle (PVN) delivery system for Abm. The transmission electron microscopic and dynamic light scattering characterization of Abm-loaded PVN (PVN(Abm)) indicated the resultant viral capsid integrity and morphology comparable to native RCNMV. In addition, the PVN(Abm) significantly increased Abm's soil mobility while enabling a controlled release strategy for Abm's bioavailability to nematodes. As a result, PVN(Abm) enlarged the zone of protection from Meloidogyne hapla root knot nematodes in the soil as compared to treating with free Abm molecules. Tomato seedlings treated with PVN(Abm) had healthier root growth and a reduction in root galling demonstrating the success of this delivery system for the increased efficacy of Abm to control nematode damage in crops.

  16. Vaccine development against the Taenia solium parasite: the role of recombinant protein expression in Escherichia coli.

    PubMed

    Gauci, Charles; Jayashi, César; Lightowlers, Marshall W

    2013-01-01

    Taenia solium is a zoonotic parasite that causes cysticercosis. The parasite is a major cause of human disease in impoverished communities where it is transmitted to humans from pigs which act as intermediate hosts. Vaccination of pigs to prevent transmission of T. solium to humans is an approach that has been investigated to control the disease. A recombinant vaccine antigen, TSOL18, has been remarkably successful at reducing infection of pigs with T. solium in several experimental challenge trials. The vaccine has been shown to eliminate transmission of naturally acquired T. solium in a field trial conducted in Africa. We recently reported that the vaccine was also effective in a field trial conducted in Peru. The TSOL18 recombinant antigen for each of these trials has been produced by expression in Escherichia coli. Here we discuss research that has been undertaken on the TSOL18 antigen and related antigens with a focus on improved methods of preparation of recombinant TSOL18 and optimized expression in Escherichia coli.

  17. Cathepsin B Cysteine Proteinase is Essential for the Development and Pathogenesis of the Plant Parasitic Nematode Radopholus similis.

    PubMed

    Li, Yu; Wang, Ke; Xie, Hui; Wang, Dong-Wei; Xu, Chun-Ling; Huang, Xin; Wu, Wen-Jia; Li, Dan-Lei

    2015-01-01

    Radopholus similis is an important plant parasitic nematode which severely harms many crops. Cathepsin B is present in a wide variety of organisms, and plays an important role in many parasites. Understanding cathepsin B of R. similis would allow us to find new targets and approaches for its control. In this study, we found that Rs-cb-1 mRNA was expressed in esophageal glands, intestines and gonads of females, testes of males, juveniles and eggs in R. similis. Rs-cb-1 expression was the highest in females, followed by juveniles and eggs, and was the lowest in males. The maximal enzyme activity of Rs-CB-1 was detected at pH 6.0 and 40 °C. Silencing of Rs-cb-1 using in vitro RNAi (Soaking with dsRNA in vitro) not only significantly inhibited the development and hatching of R. similis, but also greatly reduced its pathogenicity. Using in planta RNAi, we confirmed that Rs-cb-1 expression in nematodes were significantly suppressed and the resistance to R. similis was significantly improved in T2 generation transgenic tobacco plants expressing Rs-cb-1 dsRNA. The genetic effects of in planta RNAi-induced gene silencing could be maintained in the absence of dsRNA for at least two generations before being lost, which was not the case for the effects induced by in vitro RNAi. Overall, our results first indicate that Rs-cb-1 plays key roles in the development, hatching and pathogenesis of R. similis, and that in planta RNAi is an effective tool in studying gene function and genetic engineering of plant resistance to migratory plant parasitic nematodes.

  18. Cathepsin B Cysteine Proteinase is Essential for the Development and Pathogenesis of the Plant Parasitic Nematode Radopholus similis

    PubMed Central

    Li, Yu; Wang, Ke; Xie, Hui; Wang, Dong-Wei; Xu, Chun-Ling; Huang, Xin; Wu, Wen-Jia; Li, Dan-Lei

    2015-01-01

    Radopholus similis is an important plant parasitic nematode which severely harms many crops. Cathepsin B is present in a wide variety of organisms, and plays an important role in many parasites. Understanding cathepsin B of R. similis would allow us to find new targets and approaches for its control. In this study, we found that Rs-cb-1 mRNA was expressed in esophageal glands, intestines and gonads of females, testes of males, juveniles and eggs in R. similis. Rs-cb-1 expression was the highest in females, followed by juveniles and eggs, and was the lowest in males. The maximal enzyme activity of Rs-CB-1 was detected at pH 6.0 and 40 °C. Silencing of Rs-cb-1 using in vitro RNAi (Soaking with dsRNA in vitro) not only significantly inhibited the development and hatching of R. similis, but also greatly reduced its pathogenicity. Using in planta RNAi, we confirmed that Rs-cb-1 expression in nematodes were significantly suppressed and the resistance to R. similis was significantly improved in T2 generation transgenic tobacco plants expressing Rs-cb-1 dsRNA. The genetic effects of in planta RNAi-induced gene silencing could be maintained in the absence of dsRNA for at least two generations before being lost, which was not the case for the effects induced by in vitro RNAi. Overall, our results first indicate that Rs-cb-1 plays key roles in the development, hatching and pathogenesis of R. similis, and that in planta RNAi is an effective tool in studying gene function and genetic engineering of plant resistance to migratory plant parasitic nematodes. PMID:26221074

  19. Aminopeptidase N1 (EtAPN1), an M1 metalloprotease of the apicomplexan parasite Eimeria tenella, participates in parasite development.

    PubMed

    Gras, Simon; Byzia, Anna; Gilbert, Florence B; McGowan, Sheena; Drag, Marcin; Silvestre, Anne; Niepceron, Alisson; Lecaille, Fabien; Lalmanach, Gilles; Brossier, Fabien

    2014-07-01

    Aminopeptidases N are metalloproteases of the M1 family that have been reported in numerous apicomplexan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, and Eimeria. While investigating the potency of aminopeptidases as therapeutic targets against coccidiosis, one of the most important avian diseases caused by the genus Eimeria, we identified and characterized Eimeria tenella aminopeptidase N1 (EtAPN1). Its inhibition by bestatin and amastatin, as well as its reactivation by divalent ions, is typical of zinc-dependent metalloproteases. EtAPN1 shared a similar sequence, three-dimensional structure, and substrate specificity and similar kinetic parameters with A-M1 from Plasmodium falciparum (PfA-M1), a validated target in the treatment of malaria. EtAPN1 is synthesized as a 120-kDa precursor and cleaved into 96-, 68-, and 38-kDa forms during sporulation. Further, immunolocalization assays revealed that, similar to PfA-M1, EtAPN1 is present during the intracellular life cycle stages in both the parasite cytoplasm and the parasite nucleus. The present results support the hypothesis of a conserved role between the two aminopeptidases, and we suggest that EtAPN1 might be a valuable target for anticoccidiosis drugs.

  20. Development of a real-time PCR assay for the identification of Gyrodactylus parasites infecting salmonids in northern Europe.

    PubMed

    Collins, Catherine M; Kerr, Rose; McIntosh, Rebecca; Snow, Mike

    2010-06-11

    Gyrodactylus salaris is a monogenean freshwater parasite that causes high mortality in wild Atlantic salmon, and a number of countries employ monitoring programmes for its presence. A TaqMan-MGB (minor groove binding) probe real-time multiplex assay targeting the internal transcribed spacer ribosomal DNA (ITS rDNA) was developed to simultaneously identify G. salaris/G. thymalli and 2 other commonly occurring Gyrodactylus species infecting salmonids in northern Europe: G. derjavinoides and G. truttae. In addition, a Gyrodactylus genus-level assay was developed to assess parasite DNA quality. The species-specific real-time PCR method correctly identified target species from a wide geographical range and from a number of salmonid hosts. It did not amplify G. lucii or G. teuchis. These species were successfully amplified using the Gyrodactylus genus real-time assay. The species-specific real-time assay proved to be significantly faster than the currently employed molecular screening method of ITS rDNA PCR amplification followed by restriction fragment length polymorphism analyses (RFLP). However, as with ITS RFLP, the real-time method did not distinguish between G. salaris and the non-pathogenic G. thymalli, its principle advantage being a significant reduction in time to achieve an initial diagnostic screen before the employment of more in-depth analyses for those specimens giving a positive G. salaris/G. thymalli real-time result.

  1. Reduction of parasitic lasing

    NASA Technical Reports Server (NTRS)

    Storm, Mark E. (Inventor)

    1994-01-01

    A technique was developed which carefully retro-reflects precisely controlled amounts of light back into a laser system thereby intentionally forcing the laser system components to oscillate in a new resonator called the parasitic oscillator. The parasitic oscillator uses the laser system to provide the gain and an external mirror is used to provide the output coupling of the new resonator. Any change of gain or loss inside the new resonator will directly change the lasing threshold of the parasitic oscillator. This change in threshold can be experimentally measured as a change in the absolute value of reflectivity, provided by the external mirror, necessary to achieve lasing in the parasitic oscillator. Discrepancies between experimental data and a parasitic oscillator model are direct evidence of optical misalignment or component performance problems. Any changes in the optical system can instantly be measured as a change in threshold for the parasitic oscillator. This technique also enables aligning the system for maximum parasitic suppression with the system fully operational.

  2. Peroxiredoxins in Parasites

    PubMed Central

    Gretes, Michael C.; Poole, Leslie B.

    2012-01-01

    Abstract Significance: Parasite survival and virulence relies on effective defenses against reactive oxygen and nitrogen species produced by the host immune system. Peroxiredoxins (Prxs) are ubiquitous enzymes now thought to be central to such defenses and, as such, have potential value as drug targets and vaccine antigens. Recent Advances: Plasmodial and kinetoplastid Prx systems are the most extensively studied, yet remain inadequately understood. For many other parasites our knowledge is even less well developed. Through parasite genome sequencing efforts, however, the key players are being discovered and characterized. Here we describe what is known about the biochemistry, regulation, and cell biology of Prxs in parasitic protozoa, helminths, and fungi. At least one Prx is found in each parasite with a sequenced genome, and a notable theme is the common patterns of expression, localization, and functionality among sequence-similar Prxs in related species. Critical Issues: The nomenclature of Prxs from parasites is in a state of disarray, causing confusion and making comparative inferences difficult. Here we introduce a systematic Prx naming convention that is consistent between organisms and informative about structural and evolutionary relationships. Future Directions: The new nomenclature should stimulate the crossfertilization of ideas among parasitologists and with the broader redox research community. The diverse parasite developmental stages and host environments present complex systems in which to explore the variety of roles played by Prxs, with a view toward parlaying what is learned into novel therapies and vaccines that are urgently needed. Antioxid. Redox Signal. 17, 608–633. PMID:22098136

  3. microRNAs in parasites and parasite infection

    PubMed Central

    Zheng, Yadong; Cai, Xuepeng; Bradley, Janette E.

    2013-01-01

    miRNAs, a subclass of small regulatory RNAs, are present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. The miRNA-silencing mechanism appears, however, to be absent in a number of protozoan parasites. Protozoan miRNAs and components of their silencing machinery possess features different from other eukaryotes, providing some clues on the evolution of the RNA-induced silencing machinery. miRNA functions possibly associate with neoblast biology, development, physiology, infection and immunity of parasites. Parasite infection can alter host miRNA expression that can favor both parasite clearance and infection. miRNA pathways are, thus, a potential target for the therapeutic control of parasitic diseases. PMID:23392243

  4. microRNAs in parasites and parasite infection.

    PubMed

    Zheng, Yadong; Cai, Xuepeng; Bradley, Janette E

    2013-03-01

    miRNAs, a subclass of small regulatory RNAs, are present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. The miRNA-silencing mechanism appears, however, to be absent in a number of protozoan parasites. Protozoan miRNAs and components of their silencing machinery possess features different from other eukaryotes, providing some clues on the evolution of the RNA-induced silencing machinery. miRNA functions possibly associate with neoblast biology, development, physiology, infection and immunity of parasites. Parasite infection can alter host miRNA expression that can favor both parasite clearance and infection. miRNA pathways are, thus, a potential target for the therapeutic control of parasitic diseases.

  5. Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer

    SciTech Connect

    Evans, Elizabeth S.; Prosnitz, Robert G.; Yu Xiaoli; Zhou Sumin; Hollis, Donna R.; Wong, Terence Z.; Light, Kim L.; Hardenbergh, Patricia H.; Blazing, Michael A.; Marks, Lawrence B. . E-mail: lawrence.marks@duke.edu

    2006-11-15

    Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up 'too deep' (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI {>=}25 kg/m{sup 2} compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI {>=}25 kg/m{sup 2} may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of

  6. Parasite Carbohydrate Vaccines

    PubMed Central

    Jaurigue, Jonnel A.; Seeberger, Peter H.

    2017-01-01

    Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases—malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma, and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development. PMID:28660174

  7. Description of the first cryptic avian malaria parasite, Plasmodium homocircumflexum n. sp., with experimental data on its virulence and development in avian hosts and mosquitoes.

    PubMed

    Palinauskas, Vaidas; Žiegytė, Rita; Ilgūnas, Mikas; Iezhova, Tatjana A; Bernotienė, Rasa; Bolshakov, Casimir; Valkiūnas, Gediminas

    2015-01-01

    For over 100 years studies on avian haemosporidian parasite species have relied on similarities in their morphology to establish a species concept. Some exceptional cases have also included information about the life cycle and sporogonic development. More than 50 avian Plasmodium spp. have now been described. However, PCR-based studies show a much broader diversity of haemosporidian parasites, indicating the possible existence of a diverse group of cryptic species. In the present study, using both similarity and phylogenetic species definition concepts, we believe that we report the first characterised cryptic speciation case of an avian Plasmodium parasite. We used sequence information on the mitochondrial cytochrome b gene and constructed phylogenies of identified Plasmodium spp. to define their position in the phylogenetic tree. After analysis of blood stages, the morphology of the parasite was shown to be identical to Plasmodium circumflexum. However, the geographic distribution of the new parasite, the phylogenetic information, as well as patterns of development of infection, indicate that this parasite differs from P. circumflexum. Plasmodium homocircumflexum n. sp. was described based on information about genetic differences from described lineages, phylogenetic position and biological characters. This parasite develops parasitemia in experimentally infected birds - the domestic canary Serinus canaria domestica, siskin Carduelis spinus and crossbill Loxia curvirostra. Anaemia caused by high parasitemia, as well as cerebral paralysis caused by exoerythrocytic stages in the brain, are the main reasons for mortality. Exoerythrocytic stages also form in other organs (heart, kidneys, liver, lungs, spleen, intestines and pectoral muscles). DNA amplification was unsuccessful from faecal samples of heavily infected birds. The sporogonic development initiates, but is abortive, at the oocyst stage in two common European mosquito species, Culex pipiens pipiens (forms

  8. The Development, Clinical Signs and Economic Losses of Gastrointestinal Parasitism in Feeder Cattle on Irrigated and Non-irrigated Dikeland and Upland Pastures

    PubMed Central

    Smith, H. J.; Calder, F. W.

    1972-01-01

    Investigations were carried out over three grazing seasons with parasitized and treated (control) steers on irrigated and non-irrigated upland and dikeland pastures. The stocking rate in each paddock was adjusted by either adding or removing animals so as to maintain as uniform a sward and rate of grazing as possible. Animals were weighed on and off the pastures and fortnightly during the grazing seasons. During the first grazing season clinically normal steers shedding low numbers of gastrointestinal worm eggs contaminated the parasite-free pastures sufficiently to give rise to large residual pasture infections and clinical parasitic gastroenteritis in grazing stock during the second grazing season. Worm burdens of 100,000 to 200,000 Ostertagia ostertagi and Cooperia oncophora were established in several steers showing marked clinical signs. In spite of treatments with high dosages of thiabendazole in attempts to keep worm burdens at a minimum, there was a slow but gradual buildup of pasture infections in the paddocks grazed by the control steers over the three year period. During the second and third grazing seasons there were significant differences in the daily rate of gain between the parasitized and control animals on both upland and dikeland pastures. The parasitized groups of steers had daily rates of gain ranging from 0.29 to 0.80 pounds less than their comparable control groups. Under Maritime conditions, irrigation did not have a consistent effect on weight gains and development of parasitism. PMID:4263919

  9. Dutch perfusion incident survey.

    PubMed

    Groenenberg, Ingrid; Weerwind, Patrick W; Everts, Peter A M; Maessen, Jos G

    2010-09-01

    Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended.

  10. Parasitism, Emergence, and Development of Spalangia endius (Hymenoptera: Pteromalidae) in Pupae of Different Ages of Bactrocera cucurbitae (Diptera: Tephritidae)

    PubMed Central

    Tang, Liang-De; Ji, Xun-Cong; Han, Yun; Fu, Bu-Li; Liu, Kui

    2015-01-01

    The wasp Spalangia endius Walker (Hymenoptera: Pteromalidae) is a major parasitoid of the pupae of fruit flies, which are a common agricultural pest. An understanding of this intricate host–parasitoid interaction could provide basic information necessary for the sustainable integrated biological control of fruit flies. In this study, we investigated the effect of S. endius on different-aged pupae of the melon fly Bactrocera cucurbitae Coquillett by using choice and nonchoice tests under laboratory conditions. We showed that S. endius females oviposited, and their progeny successfully developed, in different-aged pupae of B. cucurbitae regardless of the method of exposure. There was an oviposition preference for 3–5-d-old pupa. The highest mean percentage parasitism occurred on 4- and 5-d-old hosts, followed by 2- and 3-d-old hosts. The average development time for both males and females was significantly longer in 6–7-d-old hosts than in the younger host stages. Adult females that developed from younger host pupae (2–5-d old) were significantly heavier than those from older host pupae (6–7-d old), and they also lived longer. The sex ratio (proportion of females) of the parasite progeny decreased with an increase in host age. Host mortality also decreased gradually as the pupal age increased. The differences in development time, body weight, and longevity between females and males were significant. These results suggest that S. endius is a good candidate for the biological control of B. cucurbitae. PMID:25700538

  11. Plasmid pVAX1-NH36 purification by membrane and bead perfusion chromatography.

    PubMed

    Franco-Medrano, Diana Ivonne; Guerrero-Germán, Patricia; Montesinos-Cisneros, Rosa María; Ortega-López, Jaime; Tejeda-Mansir, Armando

    2017-03-01

    The demand for plasmid DNA (pDNA) has increased in response to the rapid advances in vaccines applications to prevent and treat infectious diseases caused by virus, bacteria or parasites, such as Leishmania species. The immunization protocols require large amounts of supercoiled plasmid DNA (sc-pDNA) challenging the development of efficient and profitable processes for capturing and purified pDNA molecules from large volumes of lysates. A typical bioprocess involves four steps: fermentation, primary recovery, intermediate recovery and final purification. Ion-exchange chromatography is one of the key operations in the purification schemes of pDNA owing the chemical structure of these macromolecules. The goal of this research was to compare the performance of the final purification step of pDNA using ion-exchange chromatography on columns packed with Mustang Q membranes or perfusive beads POROS 50 HQ. The experimental results showed that both matrixes could separate the plasmid pVAX1-NH36 (3936 bp) from impurities in clarified Escherichia coli lysates with an adequate resolution. In addition, a 24- and 21-fold global purification factor was obtained. An 88 and 63% plasmid recuperation was achieved with ion-exchange membranes and perfusion beads, respectively. A better understanding of perfusion-based matrices for the purification of pDNA was developed in this research.

  12. Effect of gamma radiation on Brugia L3 development in vivo and the kinetics of granulomatous inflammation induced by these parasites.

    PubMed

    Nasarre, C; Rao, U R; Coleman, S U; Klei, T R

    1997-12-01

    Previous studies have shown that the downregulation of parasite-specific cellular immune response in Brugia-infected jirds requires viable worms but is not dependent on microfilariae (MF) for either induction or maintenance of this phenomenon. To clarify further which life cycle stages induce filarial hyporesponsiveness, jirds were infected intraperitoneally with third stage larvae (L3) exposed to 0, 15, 25, 35, 45, or 90 krad of gamma radiation to differentially alter L3 development. Necropsies were performed at 7, 14, 28, and 118 days postinoculation (DPI). The degree of parasite development, intraperitoneal inflammation, and pulmonary granulomatous inflammation (PGRN) to parasite antigen-coated beads embolized in the lungs were monitored at the time of necropsy. Parasite survival and worm lengths were inversely related to the irradiation dose. Gamma radiation at 35, 45, or 90 krad prevented larval molt to the adult stage. Some parasites irradiated with 15 or 25 krad developed beyond fourth stage larvae (L4) to infertile adult females. The PGRN peaked at 14 DPI in all infected groups. Downregulation of the PGRN occurred after 14 DPI in groups that received nonirradiated L3 or L3 irradiated with 15 krad. No significant decrease of the PGRN occurred in groups that received parasites irradiated with more than 15 krad. Significant peritoneal inflammation as indicated by an increase in macrophages occurred only in jirds that received nonirradiated L3. These data demonstrate the importance of the adult stages in inducing downmodulation in the absence of MF and suggest that the L4 may also play a role in the induction of this phenomenon. An alternate conclusion is that parasite burden and not developmental stage is important in the induction of this hyporesponsive state.

  13. [Advances on antitumor effect of parasites].

    PubMed

    Wang, Su-wen; Sun, Jun

    2014-08-01

    Immune response induced by parasites could inhibit tumor growth and promote apoptosis of tumor cells. The investigation into this character will provide new insights on the anti-tumor effect of parasites. The mechanism of parasite immune evasion may provide a reference for tumor research. Furthermore, some anti-parasitic drugs have shown antitumor effect indicating that the development of antitumor drugs may get inspiration from anti-parasitic drug studies.

  14. The Development and Evaluation of a Teleprocessed Computer-Assisted Instruction Course in the Recognition of Malarial Parasites. Final Report; May 1, 1967 - June 30, 1968.

    ERIC Educational Resources Information Center

    Mitzel, Harold E.

    A computer-assisted instruction course in the recognition of malarial parasites was developed and evaluated. The course includes stage discrimination, species discrimination, and case histories. Segments developed use COURSEWRITER as an author language and are presented via a display terminal that permits two-way communication with an IBM computer…

  15. The Development and Evaluation of a Teleprocessed Computer-Assisted Instruction Course in the Recognition of Malarial Parasites. Final Report; May 1, 1967 - June 30, 1968.

    ERIC Educational Resources Information Center

    Mitzel, Harold E.

    A computer-assisted instruction course in the recognition of malarial parasites was developed and evaluated. The course includes stage discrimination, species discrimination, and case histories. Segments developed use COURSEWRITER as an author language and are presented via a display terminal that permits two-way communication with an IBM computer…

  16. Host modulation by a parasite: how Leishmania infantum modifies the intestinal environment of Lutzomyia longipalpis to favor its development.

    PubMed

    Santos, Vania Cristina; Vale, Vladimir Fazito; Silva, Sydnei Magno; Nascimento, Alexandre Alves Sousa; Saab, Natalia Alvim Araujo; Soares, Rodrigo Pedro Pinto; Michalick, Marilene Suzan Marques; Araujo, Ricardo Nascimento; Pereira, Marcos Horacio; Fujiwara, Ricardo Toshio; Gontijo, Nelder Figueiredo

    2014-01-01

    Some reports have described the interference of Leishmania on sand flies physiology, and such behavior most likely evolved to favor the development and transmission of the parasite. Most of these studies showed that Leishmania could modulate the level of proteases in the midgut after an infective blood meal, and decreased proteolytic activity is indeed beneficial for the development of promastigotes in the gut of sand flies. In the present study, we performed a detailed investigation of the intestinal pH in Lutzomyia longipalpis females naturally infected with Leishmania infantum and investigated the production of trypsin by these insects using different approaches. Our results allowed us to propose a mechanism by which these parasites interfere with the physiology of L. longipalpis to decrease the production of proteolytic enzymes. According to our hypothesis L. infantum promastigotes indirectly interfere with the production of trypsin by modulating the mechanism that controls the intestinal pH via the action of a yet non-identified substance released by promastigote forms inside the midgut. This substance is not an acid, whose action would be restrict on to release H+ to the medium, but is a substance that is able to interfere with midgut physiology through a mechanism involving pH control. According to our hypothesis, as the pH decreases, the proteolytic enzymes efficiency is also reduced, leading to a decline in the supply of amino acids to the enterocytes: this decline reduces the stimulus for protease production because it is regulated by the supply of amino acids, thus leading to a delay in digestion.

  17. Parasites and human evolution.

    PubMed

    Perry, George H

    2014-01-01

    Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and culture. Here I review the mechanics of these and multiple other parasite proxies for human evolutionary history and discuss how they currently complement our fossil, archeological, molecular, linguistic, historical, and ethnographic records. I also highlight potential future applications of this promising model for the field of evolutionary anthropology.

  18. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  19. Improved perfusion conditions for patch-clamp recordings on human erythrocytes.

    PubMed

    Lisk, Godfrey; Desai, Sanjay A

    2006-08-18

    Various configurations of the patch-clamp method are powerful tools for examining the transport of charged solutes across biological membranes. Originally developed for the study of relatively large cells which adhere to solid surfaces under in vitro culture, these methods have been increasingly applied to small cells or organelles in suspension. Under these conditions, a number of significant technical problems may arise as a result of the smaller geometry. Here, we examined these problems using human erythrocytes infected with the malaria parasite, Plasmodium falciparum, a system where experimental differences and the technical difficulty of erythrocyte patch-clamp have hindered universal agreement on the properties of the induced ion channels. We found that patch-clamp recordings on infected erythrocytes are especially susceptible to artifacts from mechanical perturbations due to solution flow around the cell. To minimize these artifacts, we designed a new perfusion chamber whose geometry allows controlled solution flow around the fragile erythrocyte. Not only were recordings acquired in this chamber significantly less susceptible to perfusion artifacts, but the chamber permitted rapid and reversible application of known inhibitors with negligible mechanical agitation. Electrophysiological recordings then faithfully reproduced several findings made with more traditional methods. The new perfusion chamber should also be useful for patch-clamp recordings on blood cells, protoplasts, and organelles.

  20. Perfusion phantom: An efficient and reproducible method to simulate myocardial first-pass perfusion measurements with cardiovascular magnetic resonance.

    PubMed

    Chiribiri, Amedeo; Schuster, Andreas; Ishida, Masaki; Hautvast, Gilion; Zarinabad, Niloufar; Morton, Geraint; Otton, James; Plein, Sven; Breeuwer, Marcel; Batchelor, Philip; Schaeffter, Tobias; Nagel, Eike

    2013-03-01

    The aim of this article is to describe a novel hardware perfusion phantom that simulates myocardial first-pass perfusion allowing comparisons between different MR techniques and validation of the results against a true gold standard. MR perfusion images were acquired at different myocardial perfusion rates and variable doses of gadolinium and cardiac output. The system proved to be sensitive to controlled variations of myocardial perfusion rate, contrast agent dose, and cardiac output. It produced distinct signal intensity curves for perfusion rates ranging from 1 to 10 mL/mL/min. Quantification of myocardial blood flow by signal deconvolution techniques provided accurate measurements of perfusion. The phantom also proved to be very reproducible between different sessions and different operators. This novel hardware perfusion phantom system allows reliable, reproducible, and efficient simulation of myocardial first-pass MR perfusion. Direct comparison between the results of image-based quantification and reference values of flow and myocardial perfusion will allow development and validation of accurate quantification methods.

  1. Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites. 1. Quantification of hemozoin development for drug sensitive versus resistant malaria.

    PubMed

    Gligorijevic, Bojana; McAllister, Ryan; Urbach, Jeffrey S; Roepe, Paul D

    2006-10-17

    We have customized a Nipkow spinning disk confocal microscope (SDCM) to acquire three-dimensional (3D) versus time data for live, intraerythrocytic malarial parasites. Since live parasites wiggle within red blood cells, conventional laser scanning confocal microscopy produces blurred 3D images after reconstruction of z stack data. In contrast, since SDCM data sets at high x, y, and z resolution can be acquired in hundreds of milliseconds, key aspects of live parasite cellular biochemistry can be much better resolved on physiologically meaningful times scales. In this paper, we present the first 3D DIC transmittance "z stack" images of live malarial parasites and use those to quantify hemozoin (Hz) produced within the living parasite digestive vacuole, under physiologic conditions. Using live synchronized cultures and voxel analysis of sharpened DIC z stacks, we present the first quantitative in vivo analysis of the rate of Hz growth for chloroquine sensitive (CQS) versus resistant (CQR) malarial parasites. We present data for laboratory strains, as well as pfcrt transfectants expressing a CQR conferring mutant pfcrt gene. We also analyze the rate of Hz growth in the presence and absence of physiologically relevant doses of chloroquine (CQ) and verapamil (VPL) and thereby present the first in vivo quantification of key predictions from the well-known Fitch hypothesis for CQ pharmacology. In the following paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12411-12423], we acquire fluorescent images of live parasite DV via SDCM and use those to quantify DV volume for CQS versus CQR parasites.

  2. Eimeria falciformis infection of the mouse caecum identifies opposing roles of IFNγ-regulated host pathways for the parasite development.

    PubMed

    Schmid, Manuela; Heitlinger, Emanuel; Spork, Simone; Mollenkopf, Hans-Joachim; Lucius, Richard; Gupta, Nishith

    2014-07-01

    Intracellular parasites reprogram host functions for their survival and reproduction. The extent and relevance of parasite-mediated host responses in vivo remains poorly studied, however. We utilized Eimeria falciformis, a parasite infecting the mouse intestinal epithelium, to identify and validate host determinants of parasite infection. Most prominent mouse genes induced during the onset of asexual and sexual growth of parasite comprise interferon γ (IFNγ)-regulated factors, e.g., immunity-related GTPases (IRGA6/B6/D/M2/M3), guanylate-binding proteins (GBP2/3/5/6/8), chemokines (CxCL9-11), and several enzymes of the kynurenine pathway including indoleamine 2,3-dioxygenase 1 (IDO1). These results indicated a multifarious innate defense (tryptophan catabolism, IRG, GBP, and chemokine signaling), and a consequential adaptive immune response (chemokine-cytokine signaling and lymphocyte recruitment). The inflammation- and immunity-associated transcripts were increased during the course of infection, following influx of B cells, T cells, and macrophages to the parasitized caecum tissue. Consistently, parasite growth was enhanced in animals inhibited for CxCr3, a major receptor for CxCL9-11 present on immune cells. Interestingly, despite a prominent induction, mouse IRGB6 failed to bind and disrupt the parasitophorous vacuole, implying an immune evasion by E. falciformis. Furthermore, oocyst output was impaired in IFNγ-R(-/-) and IDO1(-/-) mice, both of which suggest a subversion of IFNγ signaling by the parasite to promote its growth.

  3. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  4. Development of a sampling plan in winter wheat that estimates cereal aphid parasitism levels and predicts population suppression.

    PubMed

    Giles, Kristopher L; Jones, Douglas B; Royer, Tom A; Elliott, Norman C; Kindler, S Dean

    2003-06-01

    From 1998 to 2001, the relationship between the proportion of tillers with >0 mummified aphids (Ptm) and the proportion of cereal aphids parasitized (Pp) was estimated on 57 occasions in fields of hard red winter wheat located in central and western Oklahoma. Both original (57 fields) and validation data (34 fields; 2001-2002) revealed weak relationships between Ptm and Pp, however, when Ptm > 0.1, Pp always exceeded the recommended parasitism natural enemy threshold of 0.2. Based on the relationship between Ptm and Pp, upper (Ptm1) and lower (Ptm0) decision threshold proportions were set at 0.1 and 0.02, respectively. We monitored cereal aphid populations in 16-25 winter wheat fields over time, and based on the upper and lower decision threshold proportions (Ptm1 = 0.1, Ptm0 = 0.02), predicted whether aphid intensities (# per tiller) would increase above or be maintained below selected economic thresholds (3, 9, and 15 aphids per tiller). Results of this validation study revealed that aphid intensity exceeded an economic threshold in only one field when predicted to remain below Ptm > 0.1, but aphid intensity reached a maximum of only four aphids per tiller. The sampling plan developed during this study allowed us to quickly classify Ptm, and independent of initial cereal aphid intensities, very accurately predict suppression of populations by parasitoids. Sequential sampling stop lines based on sequential probability ratio tests for classifying proportions were calculated for Ptm1 = 0.1 and Ptm0 = 0.02. A minimum of 26 tiller samples are required to classify Ptm as above 0.1 or below 0.02. Based on the results of this study, we believe that simultaneous use of aphid and parasitoid sampling plans will be efficient and useful tools for consultants and producers in the southern plains and decrease the number of unnecessary insecticide applications.

  5. Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum.

    PubMed

    Alves, Eduardo; Maluf, Fernando V; Bueno, Vânia B; Guido, Rafael V C; Oliva, Glaucius; Singh, Maneesh; Scarpelli, Pedro; Costa, Fahyme; Sartorello, Robson; Catalani, Luiz H; Brady, Declan; Tewari, Rita; Garcia, Celia R S

    2016-02-26

    In mammals, haem degradation to biliverdin (BV) through the action of haem oxygenase (HO) is a critical step in haem metabolism. The malaria parasite converts haem into the chemically inert haemozoin to avoid toxicity. We discovered that the knock-out of HO in P. berghei is lethal; therefore, we investigated the function of biliverdin (BV) and haem in the parasite. Addition of external BV and haem to P. falciparum-infected red blood cell (RBC) cultures delays the progression of parasite development. The search for a BV molecular target within the parasites identified P. falciparum enolase (Pf enolase) as the strongest candidate. Isothermal titration calorimetry using recombinant full-length Plasmodium enolase suggested one binding site for BV. Kinetic assays revealed that BV is a non-competitive inhibitor. We employed molecular modelling studies to predict the new binding site as well as the binding mode of BV to P. falciparum enolase. Furthermore, addition of BV and haem targets the phosphorylation of Plasmodium falciparum eIF2α factor, an eukaryotic initiation factor phosphorylated by eIF2α kinases under stress conditions. We propose that BV targets enolase to reduce parasite glycolysis rates and changes the eIF2α phosphorylation pattern as a molecular mechanism for its action.

  6. Emerging importance of mismatch repair components including UvrD helicase and their cross-talk with the development of drug resistance in malaria parasite.

    PubMed

    Ahmad, Moaz; Tuteja, Renu

    2014-12-01

    Human malaria is an important parasitic infection responsible for a significant number of deaths worldwide, particularly in tropical and subtropical regions. The recent scenario has worsened mainly because of the emergence of drug-resistant malaria parasites having the potential to spread across the world. Drug-resistant parasites possess a defective mismatch repair (MMR); therefore, it is essential to explore its mechanism in detail to determine the underlying cause. Recently, artemisinin-resistant parasites have been reported to exhibit nonsynonymous single nucleotide polymorphisms in genes involved in MMR pathways such as MutL homolog (MLH) and UvrD. Plasmodium falciparum MLH is an endonuclease required to restore the defective MMR in drug-resistant W2 strain of P. falciparum. Although the role of helicases in eukaryotic MMR has been questioned, the identification and characterization of the UvrD helicase and their cross-talk with MLH in P. falciparum suggests the possible involvement of UvrD in MMR. A comparative genome-wide analysis revealed the presence of the UvrD helicase in Plasmodium species, while it is absent in human host. Therefore, PfUvrD may emerge as a suitable drug target to control malaria. This review study is focused on recent developments in MMR biochemistry, emerging importance of the UvrD helicase, possibility of its involvement in MMR and the emerging cross-talk between MMR components and drug resistance in malaria parasite. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum

    PubMed Central

    Alves, Eduardo; Maluf, Fernando V.; Bueno, Vânia B.; Guido, Rafael V. C.; Oliva, Glaucius; Singh, Maneesh; Scarpelli, Pedro; Costa, Fahyme; Sartorello, Robson; Catalani, Luiz H.; Brady, Declan; Tewari, Rita; Garcia, Celia R. S.

    2016-01-01

    In mammals, haem degradation to biliverdin (BV) through the action of haem oxygenase (HO) is a critical step in haem metabolism. The malaria parasite converts haem into the chemically inert haemozoin to avoid toxicity. We discovered that the knock-out of HO in P. berghei is lethal; therefore, we investigated the function of biliverdin (BV) and haem in the parasite. Addition of external BV and haem to P. falciparum-infected red blood cell (RBC) cultures delays the progression of parasite development. The search for a BV molecular target within the parasites identified P. falciparum enolase (Pf enolase) as the strongest candidate. Isothermal titration calorimetry using recombinant full-length Plasmodium enolase suggested one binding site for BV. Kinetic assays revealed that BV is a non-competitive inhibitor. We employed molecular modelling studies to predict the new binding site as well as the binding mode of BV to P. falciparum enolase. Furthermore, addition of BV and haem targets the phosphorylation of Plasmodium falciparum eIF2α factor, an eukaryotic initiation factor phosphorylated by eIF2α kinases under stress conditions. We propose that BV targets enolase to reduce parasite glycolysis rates and changes the eIF2α phosphorylation pattern as a molecular mechanism for its action. PMID:26915471

  8. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  9. Parasitic Apologies

    ERIC Educational Resources Information Center

    Galatolo, Renata; Ursi, Biagio; Bongelli, Ramona

    2016-01-01

    The action of apologizing can be accomplished as the main business of the interaction or incidentally while participants are doing something else. We refer to these apologies as "parasitic apologies," because they are produced "en passant" (Schegloff, 2007), and focus our analysis on this type of apology occurring at the…

  10. Parasites: Water

    MedlinePlus

    ... water, they can spread the parasite into the water and continue the cycle of contamination and infection. Schistosomiasis can be spread when people swim in or have contact with freshwater lakes that are contaminated with ... drinking water or recreational water. Individuals spending time in the ...

  11. Foodborne Parasites

    USDA-ARS?s Scientific Manuscript database

    Foodborne infections are a significant cause of morbidity and mortality worldwide, and foodborne parasitic diseases, though not as widespread as bacterial and viral infections, are common on all continents and in most ecosystems, including arctic, temperate, and tropical regions. Certain foodborne ...

  12. Development of data acquisition components for simultaneous recording of 3D epicardial and surface ECG signals in the langendorff perfusion apparatus.

    PubMed

    Selby, Ryan Wade; Jonchhe, Anup; Kaplan, Chen; Lopes, Coeli M; Ghoraani, Behnaz

    2016-08-01

    Sudden Cardiac Death (SCD) claims 7 million lives per year. The importance of myocardial electrogram (EGM) repolarization alternans and surface electrocardiogram (ECG) T-wave alternans is gaining traction for understanding the underlying SCD mechanisms. However, the relationship between the 3D spatial distribution of myocardial EGMs and surface ECG with respect to SCD has yet to be investigated. To make this happen, a modified data acquisition system has been developed and fabricated in conjunction with the Langendorff perfusion system to enable simultaneous recording and analysis of the 3D spatial distribution of myocardial EGMs and the surface ECG. Two devices have been fabricated: a basket catheter, which obtains 3D EGM data; and an ECG chamber, capable of keeping the constraints of the Langendorff system. Noise analysis confirmed, for all devices, a signal to noise ratio (SNR) of median (μ) >= 51.7dB and standard deviation (σ) <;= 2.1dB. A Langendorff rat heart experiment further confirmed successful recording of 3D EGM and surface ECG data with an acceptable SNR. The developed system can be used to study the relationship between 3D EGM and surface ECG data, which can be utilized to understand the mechanisms of SCD.

  13. Gene silencing of CCD7 and CCD8 in Phelipanche aegyptiaca by tobacco rattle virus system retarded the parasite development on the host

    PubMed Central

    Aly, Radi; Dubey, Neeraj Kumar; Yahyaa, Mosaab; Abu-Nassar, Jackline; Ibdah, Mwafaq

    2014-01-01

    Strigolactones are phytohormones that stimulate seed germination of parasitic plants including Phelipanche aegyptiaca. Strigolactones are derived from carotenoids via a pathway involving the carotenoid cleavage dioxygenases CCD7 and CCD8. We report here identification of PaCCD7 and PaCCD8 orthologous genes from P. aegyptiaca. Expression analysis of PaCCD7 and PaCCD8 genes showed significant variation in their transcript levels in seeds and tubercles of P. aegyptiaca at different developmental stages. These two parasitic PaCCD7 and PaCCD8 genes were silenced in P. aegyptiaca using a trans-silencing approach in Nicotiana benthamiana. The transient knock-down of PaCCD7 and PaCCD8 inhibited tubercle development and the infestation process in host plants. Our results suggest an important role of the strigolactone associated genes (PaCCD7 and PaCCD8) in the parasite life cycle. PMID:25763619

  14. Gene silencing of CCD7 and CCD8 in Phelipanche aegyptiaca by tobacco rattle virus system retarded the parasite development on the host.

    PubMed

    Aly, Radi; Dubey, Neeraj Kumar; Yahyaa, Mosaab; Abu-Nassar, Jackline; Ibdah, Mwafaq

    2014-01-01

    Strigolactones are phytohormones that stimulate seed germination of parasitic plants including Phelipanche aegyptiaca. Strigolactones are derived from carotenoids via a pathway involving the carotenoid cleavage dioxygenases CCD7 and CCD8. We report here identification of PaCCD7 and PaCCD8 orthologous genes from P. aegyptiaca. Expression analysis of PaCCD7 and PaCCD8 genes showed significant variation in their transcript levels in seeds and tubercles of P. aegyptiaca at different developmental stages. These two parasitic PaCCD7 and PaCCD8 genes were silenced in P. aegyptiaca using a trans-silencing approach in Nicotiana benthamiana. The transient knock-down of PaCCD7 and PaCCD8 inhibited tubercle development and the infestation process in host plants. Our results suggest an important role of the strigolactone associated genes (PaCCD7 and PaCCD8) in the parasite life cycle.

  15. Gastrointestinal Parasitic Infections

    PubMed Central

    Embil, Juan A.; Embil, John M.

    1988-01-01

    This article surveys the most important gastrointestinal parasites that affect humans. The modes of acquisition, pathology, epidemiology, diagnosis, and treatment are all briefly examined. Gastrointestinal parasites have become increasingly important in the differential diagnosis of gastrointestinal disease, as a result of a number of circumstances. These circumstances include: increasing travel to developing countries; increased numbers, for one reason or another, of immunocompromised individuals; increased consumption of raw or partially cooked ethnic delicacies; more crowding in day-care centres; increased immigration from developing countries; and an endemic pocket of individuals with certain unhygienic or unsanitary practices. PMID:21253148

  16. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  17. Plants, endosymbionts and parasites

    PubMed Central

    Nagamune, Kisaburo; Xiong, Liming; Chini, Eduardo

    2008-01-01

    It was recently discovered that the protozoan parasite, Toxoplasma gondii produces and uses the plant hormone, abscisic acid (ABA), for communication. Following intracellular replication, ABA production influences the timing of parasite egress from the host cell. This density-dependent signal may serve to coordinate exit from the host cell in a synchronous manner by triggering calcium-dependent activation of motility. In the absence of ABA production, parasites undergo differentiation to the semidormant, tissue cyst. The pathway for ABA production in T. gondii may be derived from a relict endosymbiont, acquired by ingestion of a red algal cell. Although the parasite has lost the capacity for photosynthesis, the plant-like nature of this signaling pathway may be exploited to develop new drugs. In support of this idea, an inhibitor of ABA biosynthesis protected mice against lethal infection with T. gondii. Here, we compare the role of ABA in parasites to its activities in plants, where it is know to control development and stress responses. PMID:19513200

  18. Genome wide comprehensive analysis and web resource development on cell wall degrading enzymes from phyto-parasitic nematodes.

    PubMed

    Rai, Krishan Mohan; Balasubramanian, Vimal Kumar; Welker, Cassie Marie; Pang, Mingxiong; Hii, Mei Mei; Mendu, Venugopal

    2015-08-01

    The plant cell wall serves as a primary barrier against pathogen invasion. The success of a plant pathogen largely depends on its ability to overcome this barrier. During the infection process, plant parasitic nematodes secrete cell wall degrading enzymes (CWDEs) apart from piercing with their stylet, a sharp and hard mouthpart used for successful infection. CWDEs typically consist of cellulases, hemicellulases, and pectinases, which help the nematode to infect and establish the feeding structure or form a cyst. The study of nematode cell wall degrading enzymes not only enhance our understanding of the interaction between nematodes and their host, but also provides information on a novel source of enzymes for their potential use in biomass based biofuel/bioproduct industries. Although there is comprehensive information available on genome wide analysis of CWDEs for bacteria, fungi, termites and plants, but no comprehensive information available for plant pathogenic nematodes. Herein we have performed a genome wide analysis of CWDEs from the genome sequenced phyto pathogenic nematode species and developed a comprehensive publicly available database. In the present study, we have performed a genome wide analysis for the presence of CWDEs from five plant parasitic nematode species with fully sequenced genomes covering three genera viz. Bursaphelenchus, Glorodera and Meloidogyne. Using the Hidden Markov Models (HMM) conserved domain profiles of the respective gene families, we have identified 530 genes encoding CWDEs that are distributed among 24 gene families of glycoside hydrolases (412) and polysaccharide lyases (118). Furthermore, expression profiles of these genes were analyzed across the life cycle of a potato cyst nematode. Most genes were found to have moderate to high expression from early to late infectious stages, while some clusters were invasion stage specific, indicating the role of these enzymes in the nematode's infection and establishment process

  19. Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model

    PubMed Central

    Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav

    2016-01-01

    Objectives Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. Methods We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. Results In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Conclusion Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development. PMID:28005983

  20. GPU-accelerated voxelwise hepatic perfusion quantification

    NASA Astrophysics Data System (ADS)

    Wang, H.; Cao, Y.

    2012-09-01

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10-6. The method will be useful for generating liver perfusion images in clinical settings.

  1. GPU-accelerated voxelwise hepatic perfusion quantification.

    PubMed

    Wang, H; Cao, Y

    2012-09-07

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using compute unified device architecture-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, nonlinear least-squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626 400 voxels in a patient's liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10(-6). The method will be useful for generating liver perfusion images in clinical settings.

  2. GPU-Accelerated Voxelwise Hepatic Perfusion Quantification

    PubMed Central

    Wang, H; Cao, Y

    2012-01-01

    Voxelwise quantification of hepatic perfusion parameters from dynamic contrast enhanced (DCE) imaging greatly contributes to assessment of liver function in response to radiation therapy. However, the efficiency of the estimation of hepatic perfusion parameters voxel-by-voxel in the whole liver using a dual-input single-compartment model requires substantial improvement for routine clinical applications. In this paper, we utilize the parallel computation power of a graphics processing unit (GPU) to accelerate the computation, while maintaining the same accuracy as the conventional method. Using CUDA-GPU, the hepatic perfusion computations over multiple voxels are run across the GPU blocks concurrently but independently. At each voxel, non-linear least squares fitting the time series of the liver DCE data to the compartmental model is distributed to multiple threads in a block, and the computations of different time points are performed simultaneously and synchronically. An efficient fast Fourier transform in a block is also developed for the convolution computation in the model. The GPU computations of the voxel-by-voxel hepatic perfusion images are compared with ones by the CPU using the simulated DCE data and the experimental DCE MR images from patients. The computation speed is improved by 30 times using a NVIDIA Tesla C2050 GPU compared to a 2.67 GHz Intel Xeon CPU processor. To obtain liver perfusion maps with 626400 voxels in a patient’s liver, it takes 0.9 min with the GPU-accelerated voxelwise computation, compared to 110 min with the CPU, while both methods result in perfusion parameters differences less than 10−6. The method will be useful for generating liver perfusion images in clinical settings. PMID:22892645

  3. The transmission potential of malaria-infected mosquitoes (An.gambiae-Keele, An.arabiensis-Ifakara) is altered by the vertebrate blood type they consume during parasite development.

    PubMed

    Emami, S Noushin; Ranford-Cartwright, Lisa C; Ferguson, Heather M

    2017-01-17

    The efficiency of malaria parasite development within mosquito vectors (sporogony) is a critical determinant of transmission. Sporogony is thought to be controlled by environmental conditions and mosquito/parasite genetic factors, with minimal contribution from mosquito behaviour during the period of parasite development. We tested this assumption by investigating whether successful sporogony of Plasmodium falciparum parasites through to human-infectious transmission stages is influenced by the host species upon which infected mosquitoes feed. Studies were conducted on two major African vector species that generally are found to differ in their innate host preferences: Anopheles arabiensis and An. gambiae sensu stricto. We show that the proportion of vectors developing transmissible infections (sporozoites) was influenced by the source of host blood consumed during sporogony. The direction of this effect was associated with the innate host preference of vectors: higher sporozoite prevalences were generated in the usually human-specialist An. gambiae s.s. feeding on human compared to cow blood, whereas the more zoophilic An. arabiensis had significantly higher prevalences after feeding on cow blood. The potential epidemiological implications of these results are discussed.

  4. The transmission potential of malaria-infected mosquitoes (An.gambiae-Keele, An.arabiensis-Ifakara) is altered by the vertebrate blood type they consume during parasite development

    PubMed Central

    Emami, S. Noushin; Ranford-Cartwright, Lisa C.; Ferguson, Heather M.

    2017-01-01

    The efficiency of malaria parasite development within mosquito vectors (sporogony) is a critical determinant of transmission. Sporogony is thought to be controlled by environmental conditions and mosquito/parasite genetic factors, with minimal contribution from mosquito behaviour during the period of parasite development. We tested this assumption by investigating whether successful sporogony of Plasmodium falciparum parasites through to human-infectious transmission stages is influenced by the host species upon which infected mosquitoes feed. Studies were conducted on two major African vector species that generally are found to differ in their innate host preferences: Anopheles arabiensis and An. gambiae sensu stricto. We show that the proportion of vectors developing transmissible infections (sporozoites) was influenced by the source of host blood consumed during sporogony. The direction of this effect was associated with the innate host preference of vectors: higher sporozoite prevalences were generated in the usually human-specialist An. gambiae s.s. feeding on human compared to cow blood, whereas the more zoophilic An. arabiensis had significantly higher prevalences after feeding on cow blood. The potential epidemiological implications of these results are discussed. PMID:28094293

  5. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  6. Three-class ROC analysis: a sequential decision model developed for the diagnostic task rest-stress myocardial perfusion SPECT imaging

    NASA Astrophysics Data System (ADS)

    He, Xin; Frey, Eric C.

    2008-03-01

    Previously we have developed a decision model for three-class ROC analysis where classification is made three simultaneously, i.e., with a single decision. In this paper, an alternative sequential decision model was developed for the specific three-class diagnostic procedure of rest-stress myocardial perfusion SPECT (MPS) imaging. This sequential decision model was developed based on the fact that sometimes this diagnostic task is performed using a two-step process. First, the stress ( 99m Tc) image is read to determine whether a patient is normal or abnormal based on the presence of a defect in the stress image. If a defect is found, the rest ( 201Tl) image is then read to determine whether this is a reversible defect or a fixed defect based on the presence of defect on the rest image. In fact, in some MPS protocols where sequential stress/rest imaging is performed, the rest imaging is not performed if there is no defect in the stress image. Therefore, the three-class task is decomposed to a sequence of two two-class tasks. For this task we determined, by maximizing the expected utility of both steps of the decision process, that log likelihood ratios were the optimal decision variables and provide the optimal ROC surface under the assumption that incorrect decisions have equal utilities under the same hypothesis. The properties of the sequential decision model were then studied. We found that the sequential decision model shares most of the features of a 2-class ROC curve. While this model was developed in the context of rest-stress MPS, it may have applications to other two-step diagnostic tasks.

  7. Distribution of perfusion.

    PubMed

    Glenny, Robb; Robertson, H Thomas

    2011-01-01

    Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

  8. The gatekeeper residue and beyond: homologous calcium-dependent protein kinases as drug development targets for veterinarian Apicomplexa parasites.

    PubMed

    Keyloun, Katelyn R; Reid, Molly C; Choi, Ryan; Song, Yifan; Fox, Anna M W; Hillesland, Heidi K; Zhang, Zhongsheng; Vidadala, RamaSubbaRao; Merritt, Ethan A; Lau, Audrey O T; Maly, Dustin J; Fan, Erkang; Barrett, Lynn K; Van Voorhis, Wesley C; Ojo, Kayode K

    2014-09-01

    Specific roles of individual CDPKs vary, but in general they mediate essential biological functions necessary for parasite survival. A comparative analysis of the structure-activity relationships (SAR) of Neospora caninum, Eimeria tenella and Babesia bovis calcium-dependent protein kinases (CDPKs) together with those of Plasmodium falciparum, Cryptosporidium parvum and Toxoplasma gondii was performed by screening against 333 bumped kinase inhibitors (BKIs). Structural modelling and experimental data revealed that residues other than the gatekeeper influence compound-protein interactions resulting in distinct sensitivity profiles. We subsequently defined potential amino-acid structural influences within the ATP-binding cavity for each orthologue necessary for consideration in the development of broad-spectrum apicomplexan CDPK inhibitors. Although the BKI library was developed for specific inhibition of glycine gatekeeper CDPKs combined with low inhibition of threonine gatekeeper human SRC kinase, some library compounds exhibit activity against serine- or threonine-containing CDPKs. Divergent BKI sensitivity of CDPK homologues could be explained on the basis of differences in the size and orientation of the hydrophobic pocket and specific variation at other amino-acid positions within the ATP-binding cavity. In particular, BbCDPK4 and PfCDPK1 are sensitive to a larger fraction of compounds than EtCDPK1 despite the presence of a threonine gatekeeper in all three CDPKs.

  9. Development of Anti-Infectives Using Phage Display: Biological Agents against Bacteria, Viruses, and Parasites

    PubMed Central

    Huang, Johnny X.; Bishop-Hurley, Sharon L.

    2012-01-01

    The vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens. PMID:22664969

  10. Development of a DNA probe for the myxosporean parasite, Ceratomyxa shasta, using the polymerase chain reaction with arbitrary primers

    USGS Publications Warehouse

    Bartholomew, Jerri L; Rodriguez, Rusty J.; Arakawa, Cindy K.

    1995-01-01

    The arbitrarily primed polymerase chain reaction (PCR) was used to generate a DNA marker specific for the myxosporean parasite Ceratomyxa shasta. The [32~]-labeled marker hybridized to purified C. shasta DNA and to parasite DNA combined with salmonid DNA in a dot blot assay, demonstrating its potential as a diagnostic tool. The amplified DNA segment was cloned and sequenced, and primers specific for the marker were designed. When these primers were used in a standard PCR assay, DNA was amplified from C. shasta and from infected fish tissues, but not from uninfected fish tissues or from 2 other myxosporean parasites. The sensitivity of the PCR assay will permit detection of low levels of C. shasta from infected fish or oligochaetes and will be useful in defining the parasite's life cycle as well as examining its impact on salmonid populatiosn

  11. [Main parasitic skin disorders].

    PubMed

    Bernigaud, C; Monsel, G; Delaunay, P; Do-Pham, G; Foulet, F; Botterel, F; Chosidow, O

    2017-01-01

    Cutaneous parasitic skin diseases are frequent in human pathology. There are few reliable epidemiological data on the prevalence and/or incidence of such diseases. Skin parasites are cosmopolitan but their global distribution is heterogenous; prevalence is especially high in subtropical and tropical countries. They are mainly due to arthropods (insects and mites). Many species of parasites are involved, explaining the diversity of their clinical signs. The most common are caused by ectoparasites such as scabies or pediculosis (head lice, body lice and pubic lice). Clinical signs may be related to the penetration of the parasite under the skin, its development, the inoculation of venom or allergic symptoms. Diagnosis can be easy when clinical signs are pathognomonic (e.g. burrows in the interdigital web spaces in scabies) or sometimes more difficult. Some epidemiological characteristics (diurnal or nocturnal bite, seasonality) and specific clinical presentation (single or multiple bites, linear or grouped lesions) can be a great diagnostic help. Modern non-invasive tools (dermoscopy or confocal microscopy) will play an important role in the future but the eye and experience of the specialist (dermatologist, parasitologist, infectious disease specialist or entomologist) remains for the time the best way to guide or establish a diagnosis. For most skin parasites, therapeutic proposals are rarely based on studies of high level of evidence or randomized trials but more on expert recommendations or personal experience.

  12. Unexpected hosts: imaging parasitic diseases.

    PubMed

    Rodríguez Carnero, Pablo; Hernández Mateo, Paula; Martín-Garre, Susana; García Pérez, Ángela; Del Campo, Lourdes

    2017-02-01

    Radiologists seldom encounter parasitic diseases in their daily practice in most of Europe, although the incidence of these diseases is increasing due to migration and tourism from/to endemic areas. Moreover, some parasitic diseases are still endemic in certain European regions, and immunocompromised individuals also pose a higher risk of developing these conditions. This article reviews and summarises the imaging findings of some of the most important and frequent human parasitic diseases, including information about the parasite's life cycle, pathophysiology, clinical findings, diagnosis, and treatment. We include malaria, amoebiasis, toxoplasmosis, trypanosomiasis, leishmaniasis, echinococcosis, cysticercosis, clonorchiasis, schistosomiasis, fascioliasis, ascariasis, anisakiasis, dracunculiasis, and strongyloidiasis. The aim of this review is to help radiologists when dealing with these diseases or in cases where they are suspected. Teaching Points • Incidence of parasitic diseases is increasing due to migratory movements and travelling. • Some parasitic diseases are still endemic in certain regions in Europe. • Parasitic diseases can have complex life cycles often involving different hosts. • Prompt diagnosis and treatment is essential for patient management in parasitic diseases. • Radiologists should be able to recognise and suspect the most relevant parasitic diseases.

  13. Highly effective and inexpensive parasitological technique for diagnosis of intestinal parasites in developing countries: spontaneous sedimentation technique in tube.

    PubMed

    Tello, Raúl; Terashima, Angélica; Marcos, Luis A; Machicado, Jorge; Canales, Marco; Gotuzzo, Eduardo

    2012-06-01

    Millions of low-income people in the world are affected by intestinal parasites. Inexpensive, simple, and effective techniques for diagnosis are necessary. The spontaneous sedimentation technique in tube (SSTT), for application in poor healthcare settings and under field-work conditions, was described 25 years ago in Peru by Tello. The advantages of the SSTT are its ability to detect the majority of intestinal parasites, including eggs, larvae, cysts, and trophozoites, and its low cost.

  14. Developing a Model of Health Behavior Change to Reduce Parasitic Disease in Vietnam

    ERIC Educational Resources Information Center

    Petersen, Suni; Do, Trina; Shaw, Christy; Brake, Kaile

    2016-01-01

    Worldwide more deaths occur due to conditions that can be ameliorated by behavior change. Changing health behaviors using models popularized in non-western countries has not proven particularly successful. The purpose of this study was to test variables elicited during qualitative interviews and cultural conversations to develop a model of health…

  15. Hybridoma antibody immunoassays for the detection of parasitic infection: development of a model system using a larval cestode infection in mice.

    PubMed

    Mitchell, G F; Cruise, K M; Chapman, C B; Anders, R F; Howard, M C

    1979-06-01

    A prototype immunodiagnostic assay has been developed using chronic infection with the larval cestode, Mesocestoides corti, as a model system in mice. The assay is highly sensitive, it appears to be absolutely specific for M. corti infection, and is based on the inhibition of binding (by sera from infected mice) of a radiolabelled anti-M. corti hybridoma antibody to a crude M. corti antigen extract. The hybridoma antibody binds to living M. corti larvae and is an IgG1 protein. In large scale experiments no false positives were detected and the only M. corti-infected mice not detected by the assay were hypothymic nude (nu/nu) mice. Only limited success has been achieved in attempts to convert the assay to one not requiring parasite antigen and based on the inhibition of binding of radiolabelled anti-parasite hybridoma antibody and a large pool of anti-idiotype antiserum. Monoclonal antibodies derived from anti-parasite antibody-secreting hybridoma cell lines will be of particular use in the development of new, highly specific, immunodiagnostic reagents for the detection of parasite infection, exposure and disease.

  16. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    PubMed

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  17. CLONING AND FUNCTIONAL CHARACTERIZATION OF TWO CALMODULIN GENES DURING LARVAL DEVELOPMENT IN THE PARASITIC FLATWORM SCHISTOSOMA MANSONI

    PubMed Central

    Taft, Andrew S.; Yoshino, Timothy P.

    2013-01-01

    Schistosomiasis is endemic in over 70 countries in which more than 200 million people are infected with the various schistosome species. Understanding the physiological processes underlying key developmental events could be useful in developing novel chemotherapeutic reagents or infection intervention strategies. Calmodulin is a small, calcium-sensing protein found in all eukaryotes and, although the protein has been previously identified in various Schistosoma mansoni stages and implicated in egg hatching and miracidia transformation, little molecular and functional data are available for this essential protein. Herein, we report the molecular cloning, expression, and functional characterization of calmodulin in the miracidia and primary sporocyst stages of S. mansoni. Two transcripts, SmCaM1 and SmCaM2, were cloned and sequenced, and a recombinant SmCaM1 protein was expressed in Escherichia coli and used to generate anti-CaM antibodies. The 2 protein sequences were highly conserved when compared to other model organisms. The alignment of the predicted proteins of both SmCaM1 and SmCaM2 exhibited 99% identity to each other and 97–98% identity with mammalian calmodulins. Analysis of steady-state transcript abundance indicate that the 2 calmodulin transcripts differ in their stage-associated expression patterns, although the CaM protein isotype appears to be constitutively expressed during early larval development. Application of RNAi to larval parasites results in a “stunted growth” phenotype in sporocysts with 30% and 35% reduction in transcript abundance for SmCaM1 and SmCaM2, respectively, and a corresponding 35% reduction in protein level after incubation in double-stranded RNA. Differential expression of CaM transcripts during early larval development and a growth defect-inducing effect associated with partial transcript and protein inhibition as a result of RNAi, suggest a potentially important role of calmodulin during early larval development. PMID

  18. Past Intestinal Parasites.

    PubMed

    Le Bailly, Matthieu; Araújo, Adauto

    2016-08-01

    This chapter aims to provide some key points for researchers interested in the study of ancient gastrointestinal parasites. These few pages are dedicated to my colleague and friend, Prof. Adauto Araújo (1951-2015), who participated in the writing of this chapter. His huge efforts in paleoparasitology contributed to the development and promotion of the discipline during more than 30 years.

  19. The effects of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) when compared with perennial ryegrass (Lolium perenne) on ovine gastrointestinal parasite development, survival and migration.

    PubMed

    Marley, C L; Cook, R; Barrett, J; Keatinge, R; Lampkin, N H

    2006-06-15

    Two experiments were conducted to investigate the effects of birdsfoot trefoil and chicory on parasitic nematode development, survival and migration when compared with perennial ryegrass. In experiment one, sheep faeces, containing 10,385 Cooperia curticei eggs were added to 25 cm diameter pots containing birdsfoot trefoil, chicory or ryegrass, and the pots maintained under optimal conditions for nematode parasite development. Replicate pots of each forage type were destructively sampled on day 8, 16, 20, 28 and 37 to collect the nematode larvae. When forages were compared on a dry matter basis, by day 16 there were 31% and 19% fewer larvae on birdsfoot trefoil and chicory than on ryegrass, respectively (P<0.01). In the second experiment, replicate 1m(2) field plots of birdsfoot trefoil, chicory and ryegrass were sub-sampled on day 14, 21, 35 and 49 for larval counts following the application of sheep faeces containing 585,000 Teladorsagia circumcincta eggs to each plot on day 0. Results showed there were a minimum of 58% and 63% fewer infective stage parasitic larvae on birdsfoot trefoil and chicory, respectively, compared with ryegrass on day 14 and 35 when forages were compared on a forage dry matter, plot area sampled and leaf area basis (P<0.01). Overall, these results indicate that the number of infective stage larvae on birdsfoot trefoil and chicory pasture was reduced by the effect of their sward structure on the development/survival/migration of ovine parasitic nematodes. These effects may be one of the ways in which these forages may affect parasitic infections in grazing livestock.

  20. Superoxide dismutases from the oyster parasite Perkinsus marinus: purification, biochemical characterization, and development of a plate microassay for activity.

    PubMed

    Ahmed, Hafiz; Schott, Eric J; Gauthier, Julie D; Vasta, Gerardo R

    2003-07-01

    We have isolated and biochemically characterized superoxide dismutase (SOD) activity in cell extracts of clonally cultured Perkinsus marinus, a facultative intracellular parasite of the Eastern oyster, Crassostrea virginica. In order to assess the SOD activity throughout the purification, we developed and optimized a 96-well-plate microassay based on the inhibition of pyrogallol oxidation. The assay was also adapted to identify SOD activity type (Cu/Zn-, Mn-, or FeSOD), even in mixtures of more than one type of SOD. All SOD activity detected in the cell extracts was of the FeSOD type. Most of the SOD activity in P. marinus trophozoites resides in a major component of subunit molecular weight 24 kDa. The protein was purified by affinity chromatography on an anti-SOD antibody-Sepharose column. Amino-terminal peptide sequence of the affinity-purified protein corresponds to the predicted product of the PmSOD1 gene and indicates that amino-terminal processing has taken place. The results are discussed in the context of processing of mitochondrially targeted SODs.

  1. Attenuation of a drug-sensitive strain of a turkey protozoan parasite Eimeria meleagrimitis by selection for precocious development.

    PubMed

    Rathinam, T; Gadde, U; Chapman, H D

    2016-01-30

    An attenuated line of Eimeria meleagrimitis was established by repeated propagation of the parasite in 9-day old turkey poults and subsequent selection for precocious development. Following 20 passages, the prepatent period decreased from 120 to 104h. A series of experiments were conducted to evaluate the pathogenicity, immunogenicity and fecundity of the newly selected line. Judged by body weight gain, feed consumption and feed efficiency following infection, the attenuated line had appreciably reduced pathogenicity. Immunogenicity of the attenuated line was examined by infecting poults successively with incremental doses of 10(2), 10(3) and 10(4) oocysts at 0, 7, and 14 days of age respectively. No oocysts were detected following challenge with 5×10(2) oocysts, indicating that the attenuated line had retained immunogenicity. Fecundity was assessed by infecting two-week old birds with 5×10(2) oocysts of either parent or attenuated line. Oocyst production from 96 to 240h post-infection showed that the patent period of the attenuated line commenced earlier and was of shorter duration than the parent line.

  2. Serine Proteases of Parasitic Helminths

    PubMed Central

    Yang, Yong; Wen, Yun jun; Cai, Ya Nan; Vallée, Isabelle; Boireau, Pascal; Liu, Ming Yuan; Cheng, Shi Peng

    2015-01-01

    Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed. PMID:25748703

  3. Development of transgenic fungi that kill human malaria parasites in mosquitoes.

    PubMed

    Fang, Weiguo; Vega-Rodríguez, Joel; Ghosh, Anil K; Jacobs-Lorena, Marcelo; Kang, Angray; St Leger, Raymond J

    2011-02-25

    Metarhizium anisopliae infects mosquitoes through the cuticle and proliferates in the hemolymph. To allow M. anisopliae to combat malaria in mosquitoes with advanced malaria infections, we produced recombinant strains expressing molecules that target sporozoites as they travel through the hemolymph to the salivary glands. Eleven days after a Plasmodium-infected blood meal, mosquitoes were treated with M. anisopliae expressing salivary gland and midgut peptide 1 (SM1), which blocks attachment of sporozoites to salivary glands; a single-chain antibody that agglutinates sporozoites; or scorpine, which is an antimicrobial toxin. These reduced sporozoite counts by 71%, 85%, and 90%, respectively. M. anisopliae expressing scorpine and an [SM1](8):scorpine fusion protein reduced sporozoite counts by 98%, suggesting that Metarhizium-mediated inhibition of Plasmodium development could be a powerful weapon for combating malaria.

  4. Development of parasitic Maculinea teleius (Lepidoptera, Lycaenidae) larvae in laboratory nests of four Myrmica ant host species.

    PubMed

    Witek, M; Skórka, P; Sliwińska, E B; Nowicki, P; Moroń, D; Settele, J; Woyciechowski, M

    2011-08-01

    Maculinea butterflies are social parasites of Myrmica ants. Methods to study the strength of host ant specificity in the Maculinea-Myrmica association include research on chemical and acoustic mimicry as well as experiments on ant adoption and rearing behaviour of Maculinea larvae. Here we present results of laboratory experiments on adoption, survival, development and integration of M. teleius larvae within the nests of different Myrmica host species, with the objective of quantifying the degree of specialization of this Maculinea species. In the laboratory, a total of 94 nests of four Myrmica species: M. scabrinodis, M. rubra, M.ruginodis and M. rugulosa were used. Nests of M. rubra and M. rugulosa adopted M. teleius larvae more readily and quickly than M. ruginodis colonies. No significant differences were found in the survival rates of M. teleius larvae reared by different ant species. Early larval growth of M. teleius larvae differed slightly among nests of four Myrmica host species. Larvae reared by colonies of M. rugulosa which were the heaviest at the beginning of larval development had the lowest mean larval body mass after 18 weeks compared to those reared by other Myrmica species. None of the M.teleius larvae was carried by M. scabrinodis or M. rubra workers after ant nests were destroyed, which suggests a lack of integration with host colonies. Results indicate that Myrmica species coming from the same site differ in their ability to adopt and rear M. teleius larvae but there was no obvious adaptation of this butterfly species to one of the host ant species. This may explain why, under natural conditions, all four ants can be used as hosts of this butterfly species. Slight advantages of particular Myrmica species as hosts at certain points in butterfly larval development can be explained by the ant species biology and colony structure rather than by specialization of M. teleius.

  5. Evolutionary consequence of a change in life cycle complexity: A link between precocious development and evolution toward female-biased sex allocation in a hermaphroditic parasite.

    PubMed

    Kasl, Emily L; McAllister, Chris T; Robison, Henry W; Connior, Matthew B; Font, William F; Criscione, Charles D

    2015-12-01

    The evolutionary consequences of changes in the complex life cycles of parasites are not limited to the traits that directly affect transmission. For instance, mating systems that are altered due to precocious sexual maturation in what is typically regarded as an intermediate host may impact opportunities for outcrossing. In turn, reproductive traits may evolve to optimize sex allocation. Here, we test the hypothesis that sex allocation evolved toward a more female-biased function in populations of the hermaphroditic digenean trematode Alloglossidium progeneticum that can precociously reproduce in their second hosts. In these precocious populations, parasites are forced to self-fertilize as they remain encysted in their second hosts. In contrast, parasites in obligate three-host populations have more opportunities to outcross in their third host. We found strong support that in populations with precocious development, allocation to male resources was greatly reduced. We also identified a potential phenotypically plastic response in a body size sex allocation relationship that may be driven by the competition for mates. These results emphasize how changes in life cycle patterns that alter mating systems can impact the evolution of reproductive traits in parasites. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  6. Development of a Multiplex PCR-Ligase Detection Reaction Assay for Diagnosis of Infection by the Four Parasite Species Causing Malaria in Humans

    PubMed Central

    McNamara, David T.; Thomson, Jodi M.; Kasehagen, Laurin J.; Zimmerman, Peter A.

    2004-01-01

    The diagnosis of infections caused by Plasmodium species is critical for understanding the nature of malarial disease, treatment efficacy, malaria control, and public health. The demands of field-based epidemiological studies of malaria will require faster and more sensitive diagnostic methods as new antimalarial drugs and vaccines are explored. We have developed a multiplex PCR-ligase detection reaction (LDR) assay that allows the simultaneous diagnosis of infection by all four parasite species causing malaria in humans. This assay exhibits sensitivity and specificity equal to those of other PCR-based assays, identifying all four human malaria parasite species at levels of parasitemias equal to 1 parasitized erythrocyte/μl of blood. The multiplex PCR-LDR assay goes beyond other PCR-based assays by reducing technical procedures and by detecting intraindividual differences in species-specific levels of parasitemia. Application of the multiplex PCR-LDR assay will provide the sensitivity and specificity expected of PCR-based diagnostic assays and will contribute new insight regarding relationships between the human malaria parasite species and the human host in future epidemiological studies. PMID:15184411

  7. Development of a multiplex PCR-ligase detection reaction assay for diagnosis of infection by the four parasite species causing malaria in humans.

    PubMed

    McNamara, David T; Thomson, Jodi M; Kasehagen, Laurin J; Zimmerman, Peter A

    2004-06-01

    The diagnosis of infections caused by Plasmodium species is critical for understanding the nature of malarial disease, treatment efficacy, malaria control, and public health. The demands of field-based epidemiological studies of malaria will require faster and more sensitive diagnostic methods as new antimalarial drugs and vaccines are explored. We have developed a multiplex PCR-ligase detection reaction (LDR) assay that allows the simultaneous diagnosis of infection by all four parasite species causing malaria in humans. This assay exhibits sensitivity and specificity equal to those of other PCR-based assays, identifying all four human malaria parasite species at levels of parasitemias equal to 1 parasitized erythrocyte/microl of blood. The multiplex PCR-LDR assay goes beyond other PCR-based assays by reducing technical procedures and by detecting intraindividual differences in species-specific levels of parasitemia. Application of the multiplex PCR-LDR assay will provide the sensitivity and specificity expected of PCR-based diagnostic assays and will contribute new insight regarding relationships between the human malaria parasite species and the human host in future epidemiological studies.

  8. The Effect of Temperature on Synchronization of Brood Development of the Bopyrid Isopod Parasite Probopyrus pandalicola with Molting of Its Host, the Daggerblade Grass Shrimp Palaemonetes pugio.

    PubMed

    Brinton, Brigette A; Curran, Mary Carla

    2015-08-01

    The bopyrid isopod Probopyrus pandalicola is a hematophagous ectoparasite that sexually sterilizes some palaemonid shrimps, including female daggerblade grass shrimp Palaemonetes pugio. The reproduction of parasitic isopods is thought to occur synchronously with host molting because the brood would be unsuccessful if molting occurred before the larvae were free swimming. Temperature affects the length of the molting cycle of shrimp, and therefore may also affect the incubation time of isopod broods. The purpose of the present study was to determine the effect of temperature on brood development of the parasite and on the degree of synchronization with the molting of its host. Parasitized P. pugio were monitored daily at 2 experimental temperatures, 23 and 15 C, in temperature-controlled chambers for the duration of a full parasite reproductive cycle. Developmental stage was determined by the visible coloration of the brood through the exoskeleton of the host, and was designated as egg, embryo I, embryo II, or epicaridium larvae. Temperature significantly affected median brood incubation time, which was only 11 days at 23 C, as compared to 35 days at 15 C. The final developmental stage (epicaridium larvae) was 3 times shorter at 23 C (median 3 days; n = 45) than at 15 C (median 9 days; n = 15). Temperature significantly affected the intermolt period of parasitized shrimp, which was shorter at 23 C (median 12 days) than at 15 C (median 37 days). A smaller percentage of the intermolt period elapsed between larval release and shrimp molting at 23 C (0.0%) than at 15 C (3.1%), indicating closer synchronization between host molting and parasite reproduction at the warmer temperature. At 15 C, the isopods utilized a smaller proportion of the time that was available for brood incubation during the intermolt period of their host. Brood size ranged from 391 to 4,596 young and was positively correlated with parasite and host size. Because development progressed more rapidly

  9. Terpenes Arrest Parasite Development and Inhibit Biosynthesis of Isoprenoids in Plasmodium falciparum

    PubMed Central

    Rodrigues Goulart, Herbert; Kimura, Emília A.; Peres, Valnice J.; Couto, Alicia S.; Aquino Duarte, Fulgencio A.; Katzin, Alejandro M.

    2004-01-01

    Development of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized in P. falciparum. These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure to the intermediates of the isoprenoids pathway, as potential antimalarial drugs. Different terpenes and S-farnesylthiosalicylic acid were tested on cultures of the intraerythrocytic stages of P. falciparum, and the 50% inhibitory concentrations for each one were found: farnesol, 64 μM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; and S-farnesylthiosalicylic acid, 14 μM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(n)-3H]farnesyl pyrophosphate triammonium salt ([3H]FPP) was used as precursor. Farnesol, nerolidol, and linalool showed stronger inhibitory activity on the biosynthesis of the isoprenic side chain of the benzoquinone ring of ubiquinones in the schizont stage. Treatment of schizont stages with S-farnesylthiosalicylic acid led to a decrease in intensity of the band corresponding a p21ras protein. The inhibitory effect of terpenes and S-farnesylthiosalicylic acid on the biosynthesis of both dolichol and the isoprenic side chain of ubiquinones and the isoprenylation of proteins in the intraerythrocytic stages of P. falciparum appears to be specific, because overall protein biosynthesis was not affected. Combinations of some terpenes or S-farnesylthiosalicylic acid tested in this work with other antimalarial drugs, like fosmidomycin, could be a new strategy for the treatment of malaria. PMID:15215101

  10. Babesia parasites develop and are transmitted by the non-vector soft tick Ornithodoros moubata (Acari: Argasidae).

    PubMed

    Battsetseg, B; Matsuo, T; Xuan, X; Boldbaatar, D; Chee, S H; Umemiya, R; Sakaguchi, T; Hatta, T; Zhou, J; Verdida, A R; Taylor, D; Fujisaki, K

    2007-01-01

    Ornithodoros moubata ticks were fed on blood infected with Babesia equi. However, the parasites were quickly cleared as evidenced by the disappearance of B. equi-specific ribosomal RNA from the ticks. We hypothesized that if the Babesia parasite can escape midgut-associated barriers a non-vector tick can become infected with Babesia. To test this hypothesis, B. equi parasite-infected blood from in vitro culture was injected into the haemocoel of ticks. B. equi-specific rRNA was surprisingly detected 45 days after injection even in the eggs. Babesia-free dogs were infested with O. moubata ticks that were infected by inoculation with B. gibsoni-infected red blood cells. Parasitaemia and antibody production against Bg-TRAP of B. gibsoni increased gradually. These results indicate that O. moubata may be a useful vector model for Babesia parasites and also a very important tool for studies on tick immunity against Babesia parasites and tick-Babesia interactions.

  11. Perfusion abnormalities in hemimegalencephaly.

    PubMed

    Wintermark, P; Roulet-Perez, E; Maeder-Ingvar, M; Moessinger, A C; Gudinchet, F; Meuli, R

    2009-04-01

    Cerebrovascular changes are rarely discussed in patients with hemimegalencephaly. These alterations have previously been associated with epileptical activity. We report the case of a 36-week gestation neonate presenting with total right hemimegalencephaly, as demonstrated by a magnetic resonance imaging (MRI) performed in the first days of life. Perfusion-weighted imaging displayed a clear hypervascularization of the right hemisphere. Diffusion-tensor imaging showed an arrangement of white matter fibers concentrically around the ventricle on the right hemisphere. AngioMRI showed an obvious asymmetry in the size of the middle cerebral arteries, with the right middle cerebral artery being prominent. The baby was free of clinical seizures during his first week of life. An electroencephalogram at that time displayed an asymmetric background activity, but no electrical seizures. Perfusion anomalies in hemimegalencephaly may not necessarily be related to epileptical activity, but may be related to vessel alterations. (c) Georg Thieme Verlag KG Stuttgart, New York.

  12. Trichinella spiralis: Adaptation and parasitism.

    PubMed

    Zarlenga, Dante; Wang, Zhengyuan; Mitreva, Makedonka

    2016-11-15

    , especially those involved in sensory perception, metabolism, and transcription/translation. New protein gains with functions related to regulating transcription and translation, and protein family expansions with functions related to morphology and body development have occurred in association with parasitism. Further gains occurred as a result of lateral gene transfer and in particular, with the cyanase protein family In contrast, reductions and/or losses have occurred in protein families with functions related to metabolic process and signal transduction. Taking advantage of the independent occurrences of parasitism in nematodes, which enabled us to distinguish changes associated with parasitism from species specific niche adaptation, our study provides valuable insights into nematode parasitism at a proteome level using T. spiralis as a benchmark for early adaptation to or acquisition of parasitism. Published by Elsevier B.V.

  13. Emerging food-borne parasites.

    PubMed

    Dorny, P; Praet, N; Deckers, N; Gabriel, S

    2009-08-07

    -borne trematode is the lungfluke (Paragonimus spp.). Traditionally, these parasitic zoonoses are most common in Asia because of the particular food practices and the importance of aquaculture. However, some of these parasites may emerge in other continents through aquaculture and improved transportation and distribution systems. Because of inadequate systems for routine diagnosis and monitoring or reporting for many of the zoonotic parasites, the incidence of human disease and parasite occurrence in food is underestimated. Of particular concern in industrialised countries are the highly resistant waterborne protozoal infections as well as the increased travel and immigration, which increase the exposure to exotic diseases. The increased demand for animal proteins in developing countries will lead to an intensification of the production systems in which the risk of zoonotic infections needs to be assessed. Overall, there is an urgent need for better monitoring and control of food-borne parasites using new technologies.

  14. DEVELOPMENT AND APPLICATION OF AN eDNA METHOD TO DETECT AND QUANTIFY A PATHOGENIC PARASITE IN AQUATIC ECOSYSTEMS

    PubMed Central

    Huver, J. R.; Koprivnikar, J.; Johnson, P. T. J.; Whyard, S.

    2015-01-01

    Approaches based on organismal DNA found in the environment (eDNA) have become increasingly utilized for ecological studies and biodiversity inventories as an alternative to traditional field survey methods. Such DNA-based techniques have been largely used to establish the presence of free-living organisms, but have much potential for detecting and quantifying infectious agents in the environment, which are necessary to evaluate disease risk. We developed an eDNA method to examine the distribution and abundance of the trematode Ribeiroia ondatrae, a pathogenic parasite known to cause malformations in North American amphibians. In addition to comparing this eDNA approach to classical host necropsy, we examined the detectability of R. ondatrae in water samples subject to different degradation conditions (time and temperature). Our test exhibited high specificity and sensitivity to R. ondatrae, capable of detecting as little as 14 fg of this parasite’s DNA (1/2500th of a single infectious stage) from field water samples. Compared to our results from amphibian host necropsy, quantitative PCR was ∼ 90% concordant with respect to R. ondatrae detection from 15 field sites and was also a significant predictor of host infection abundance. DNA was still detectable in lab samples after 21 days at 25 °C, indicating that our method is robust to field conditions. By comparing the advantages and disadvantages of eDNA versus traditional survey methods for determining pathogen presence and abundance in the field, we found that the lower costs and effort associated with eDNA approaches provide many advantages. The development of alternative tools is critical for disease ecology as wildlife management and conservation efforts require reliable establishment and monitoring of pathogens. PMID:26380540

  15. Development of a NIRS method to quantify cerebral perfusion and oxidative metabolism in preterm infants with post-hemorrhagic ventricle dilation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    McLachlan, Peter; Kishimoto, Jessica; de Ribeaupierre, Sandrine; Lee, David S. C.; Diop, Mamadou; St Lawrence, Keith

    2017-02-01

    A complication of intraventricular hemorrhage among preterm neonates is post-hemorrhagic ventricle dilation (PHVD), which is associated with a greater risk of life-long neurological disability. Clinical evidence, including suppressed EEG patterns, suggests that cerebral perfusion and oxygenation is impaired in these patients, likely due to elevated intracranial pressure (ICP). Cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2) can be quantified by dynamic contrast-enhanced NIRS; however, PHVD poses a unique challenge to NIRS since the cerebral mantle can be compressed to 1 cm or less. The objectives of this work were to develop a finite-slab model for the analysis of NIRS spectra, incorporating depth measurements from ultrasound images, and to assess the magnitude of error when using the standard semi-infinite model. CBF, tissue saturation (StO2) and CMRO2 were measured in 9 patients receiving ventricle taps to reduce ICP. Monte Carlo simulations indicated that errors in StO2 could be greater than 20% if the cerebral mantle was reduced to 1 cm. Using the finite-slab model, basal CBF and CMRO2 in the PHVD patients were not significantly different from a control group of preterm infants (14.6 ± 4.2 ml/100 g/min and 1.0 ± 0.4 ml O2/100 g/min), but StO2 was significantly lower (PDA 70.5 ± 9%, PHVD 58.9 ± 12%). Additionally, ventricle tapping improved CBF by 15.6 ± 22%. This work indicates that applying NIRS to PHVD patients is prone to error; however, this issue can be overcome with the appropriate model and using readily available ultrasound images.

  16. Myocardial perfusion as an indicator of graft patency after coronary artery bypass surgery. [Thallium 201

    SciTech Connect

    Kolibash, A.J.; Call, T.D.; Bush, C.A.; Tetalman, M.R.; Lewis, R.P.

    1980-05-01

    Stress and resting myocardial perfusion were assessed in 38 patients who received 96 grafts. Stress perfusion was evaluated with thallium-201 and resting myocardial blood flow distribution with radiolabeled particles. When both stress and rest perfusion were normal, graft patency was 82% (51 of 62 grafts). Graft patency was also high (81%, 13 of 16) in areas where stress perfusion abnormalities resolved or become less apparent at rest. However, when stress perfusion defects remained unchanged at rest, the graf was likely to be occuluded (73%, 11 of 15). Maintenance of normal rest perfusion or improvement of rest perfusion postoperatively was also associated with a high graft patency rate (80%, 35 of 44), whereas the development of new rest perfusion defects postoperatively implied graft occlusion (86%, six of seven).

  17. Development of Kit Formulations for 99mTcN-MPO: A Cationic Radiotracer for Myocardial Perfusion Imaging

    PubMed Central

    Zheng, Yumin; Ji, Shundong; Tomaselli, Elena; Liu, Shuang

    2015-01-01

    The objective of this study was to develop a kit formulation for 99mTcN-MPO to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two-vial formulation and single-vial formulations with/without SnCl2) to explore the factors influencing radiochemical purity (RCP) of 99mTcN-MPO. We found that the most important factor affecting the RCP of 99mTcN-MPO was the purity of PNP5. 99mTcN-MPO was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial formulations with/without SnCl2, β-cyclodextrin (β-CD) is particularly useful as a stabilizer for PNP5. The RCP of 99mTcN-MPO was 95 – 98% using β-CD, but its RCP was only 90 – 93% with γ-CD. It seems that PNP5 fits better into the inner cavity of β-CD, which forms more stable inclusion complex than γ-CD in the single-vial formulations. The results from biodistribution and imaging studies in Sprague-Dawley (SD) rats clearly demonstrated biological equivalence of three different formulations. SPECT data suggested that high quality images could be obtained at 0 – 30 min post-injection without significant interference from the liver radioactivity. Considering the ease for 99mTc-labeling and high RCP of 99mTcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies. PMID:25070025

  18. Fossils of parasites: what can the fossil record tell us about the evolution of parasitism?

    PubMed

    Leung, Tommy L F

    2017-02-01

    Parasites are common in many ecosystems, yet because of their nature, they do not fossilise readily and are very rare in the geological record. This makes it challenging to study the evolutionary transition that led to the evolution of parasitism in different taxa. Most studies on the evolution of parasites are based on phylogenies of extant species that were constructed based on morphological and molecular data, but they give us an incomplete picture and offer little information on many important details of parasite-host interactions. The lack of fossil parasites also means we know very little about the roles that parasites played in ecosystems of the past even though it is known that parasites have significant influences on many ecosystems. The goal of this review is to bring attention to known fossils of parasites and parasitism, and provide a conceptual framework for how research on fossil parasites can develop in the future. Despite their rarity, there are some fossil parasites which have been described from different geological eras. These fossils include the free-living stage of parasites, parasites which became fossilised with their hosts, parasite eggs and propagules in coprolites, and traces of pathology inflicted by parasites on the host's body. Judging from the fossil record, while there were some parasite-host relationships which no longer exist in the present day, many parasite taxa which are known from the fossil record seem to have remained relatively unchanged in their general morphology and their patterns of host association over tens or even hundreds of millions of years. It also appears that major evolutionary and ecological transitions throughout the history of life on Earth coincided with the appearance of certain parasite taxa, as the appearance of new host groups also provided new niches for potential parasites. As such, fossil parasites can provide additional data regarding the ecology of their extinct hosts, since many parasites have

  19. Mapping the literature of perfusion.

    PubMed Central

    Hall, E F

    1999-01-01

    Perfusionists select and operate the equipment necessary for monitoring, supporting, or temporarily replacing the patient's circulatory or respiratory function. There are over 3,000 perfusionists working in U.S. hospitals, medical and perfusionist groups, and as independent contractors. The purpose of this study was to identify the core literature of perfusion and to determine which major databases provide the most thorough access to this literature. This paper is part of the Medical Library Association Nursing and Allied Health Resource Section's project to map the literature of the allied health professions. It uses a bibliometric methodology to identify core journals. A group of forty-three journals was determined to make up the core journal literature of perfusion. MEDLINE provided the best overall indexing coverage for these journals, but librarians and perfusionists will wish to supplement its use with the Cumulative Index to Nursing and Allied Health Literature in order to access the journals written primarily for perfusionists. The study results can guide purchasing and database searching decisions of collection development and reference librarians, encourage the database producer to increase coverage of titles that are unindexed or underindexed, and advise perfusionists of the best access to their core literature. PMID:10427432

  20. Automated quantitative analysis of ventilation-perfusion lung scintigrams

    SciTech Connect

    Burton, G.H.; Vernon, P.; Seed, W.A.

    1984-05-01

    An automated computer analysis of ventilation (Kr-81m) and perfusion (Tc-99m) lung images has been devised that produces a graphical image of the distribution of ventilation and perfusion, and of ventilation-perfusion ratios. The analysis has overcome the following problems: the identification of the midline between two lungs and the lung boundaries, the exclusion of extrapulmonary radioactivity, the superimposition of lung images of different sizes, and the format for presentation of the data. Therefore, lung images of different sizes and shapes may be compared with each other. The analysis has been used to develop normal ranges from 55 volunteers. Comparison of younger and older age groups of men and women show small but significant differences in the distribution of ventilation and perfusion, but no differences in ventilation-perfusion ratios.

  1. Induction of Haustorium Development by Sphaeropsidones in Radicles of the Parasitic Weeds Striga and Orobanche. A Structure-Activity Relationship Study.

    PubMed

    Fernández-Aparicio, Mónica; Masi, Marco; Maddau, Lucia; Cimmino, Alessio; Evidente, Marco; Rubiales, Diego; Evidente, Antonio

    2016-06-29

    Crop attack by parasitic weeds such as Striga and Orobanche occurs through developmental processes triggered by host chemodetection. Seeds of those weed species remain dormant in the soil until germination is triggered by host root exudates. The development of haustorium, a parasitic plant organ that invades the host to withdraw its nutrients, is also initiated in Orobanchaceae by host molecular cues. The induction of haustorium development by exogenous signals has previously been reported for Striga but not for Orobanche species. In this work, we demonstrate that sphaeropsidone and epi-sphaeropsidone, two phytotoxic cyclohexene oxides isolated from the fungus Diplodia cupressi, a causal agent of cypress canker, induce haustorium development in radicles of the parasitic weeds Striga hermonthica, Orobanche crenata, and Orobanche cumana. This is the first report of chemical stimulation of haustorium development in radicles of Orobanche in the absence of host. In addition, SAR studies were carried out by testing the haustorium-inducing activity of the natural cyclohexene oxides, seven already known and four new hemisynthetic derivatives, in O. cumana, O. crenata, and S. hermonthica, to find a molecular specificity model required for haustorium induction. The results suggested that the haustorium-inducing activity is due to the possibility to convert the natural sphaeropsidone and natural and hemisynthetic derivatives in the corresponding 3-methoxyquinone and that the stereochemistry at C-5 also seems to affect this activity.

  2. The life cycle of Gregarina cuneata in the midgut of Tribolium castaneum and the effects of parasitism on the development of insects.

    PubMed

    Gigliolli, A A S; Julio, A H F; Conte, H

    2016-04-01

    Tribolium castaneum Herbst 1797 (Coleoptera: Tenebrionidae), an important pest of stored grains and byproducts, is naturally infected by Gregarina cuneata Stein 1848 (Apicomplexa: Gregarinidae). Changes in the life cycle of insects caused by the parasite development in the midgut were studied. Trophozoites, gamonts (solitary and associated), and gametocysts were present in the midgut of the insects. In young trophozoites, the apical region differentiated into an epimerite that firmly attached the parasite to the host epithelial cells. With maturation, trophozoites developed in gamonts that were associated with the initiation of sexual reproduction in the cell cycle, culminating in the formation of the spherical gametocyst. Morpho-functional analyses indicated that gregarines absorb nutrients from infected cells and can occlude the midgut as they develop. Consequently, nutritional depletion may interfere with the host's physiology, causing decreased growth, delayed development, and high mortality rates of the parasitized insects. These results suggest G. cuneata could be an important biological agent for controlling T. castaneum in integrated pest management programs.

  3. Variability in quantitative cardiac magnetic resonance perfusion analysis

    PubMed Central

    Bratis, K.

    2013-01-01

    By taking advantage of its high spatial resolution, noninvasive and nontoxic nature first-pass perfusion cardiovascular magnetic resonance (CMR) has rendered an indispensable tool for the noninvasive detection of reversible myocardial ischemia. A potential advantage of perfusion CMR is its ability to quantitatively assess perfusion reserve within a myocardial segment, as expressed semi- quantitatively by myocardial perfusion reserve index (MPRI) and fully- quantitatively by absolute myocardial blood flow (MBF). In contrast to the high accuracy and reliability of CMR in evaluating cardiac function and volumes, perfusion CMR is adversely affected by multiple potential reasons during data acquisition as well as post-processing. Various image acquisition techniques, various contrast agents and doses as well as variable blood flow at rest as well as variable reactions to stress all influence the acquired data. Mechanisms underlying the variability in perfusion CMR post processing, as well as their clinical significance, are yet to be fully elucidated. The development of a universal, reproducible, accurate and easily applicable tool in CMR perfusion analysis remains a challenge and will substantially enforce the role of perfusion CMR in improving clinical care. PMID:23825774

  4. Genomics of apicomplexan parasites.

    PubMed

    Swapna, Lakshmipuram Seshadri; Parkinson, John

    2017-02-22

    The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.

  5. Perfusion Based Cell Culture Chips

    NASA Astrophysics Data System (ADS)

    Heiskanen, A.; Emnéus, J.; Dufva, M.

    Performing cell culture in miniaturized perfusion chambers gives possibilities to experiment with cells under near in vivo like conditions. In contrast to traditional batch cultures, miniaturized perfusion systems provide precise control of medium composition, long term unattended cultures and tissue like structuring of the cultures. However, as this chapter illustrates, many issues remain to be identified regarding perfusion cell culture such as design, material choice and how to use these systems before they will be widespread amongst biomedical researchers.

  6. Neutrophils clear bacteria associated with parasitic nematodes augmenting the development of an effective Th2-type response

    USDA-ARS?s Scientific Manuscript database

    Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node w...

  7. Sequence variation and structural conservation allows development of novel function and immune evasion in parasite surface protein families.

    PubMed

    Higgins, Matthew K; Carrington, Mark

    2014-04-01

    Trypanosoma and Plasmodium species are unicellular, eukaryotic pathogens that have evolved the capacity to survive and proliferate within a human host, causing sleeping sickness and malaria, respectively. They have very different survival strategies. African trypanosomes divide in blood and extracellular spaces, whereas Plasmodium species invade and proliferate within host cells. Interaction with host macromolecules is central to establishment and maintenance of an infection by both parasites. Proteins that mediate these interactions are under selection pressure to bind host ligands without compromising immune avoidance strategies. In both parasites, the expansion of genes encoding a small number of protein folds has established large protein families. This has permitted both diversification to form novel ligand binding sites and variation in sequence that contributes to avoidance of immune recognition. In this review we consider two such parasite surface protein families, one from each species. In each case, known structures demonstrate how extensive sequence variation around a conserved molecular architecture provides an adaptable protein scaffold that the parasites can mobilise to mediate interactions with their hosts. © 2014 The Protein Society.

  8. Development and Validation of a Biodynamic Model for Mechanistically Predicting Metal Accumulation in Fish-Parasite Systems.

    PubMed

    Le, T T Yen; Nachev, Milen; Grabner, Daniel; Hendriks, A Jan; Sures, Bernd

    2016-01-01

    Because of different reported effects of parasitism on the accumulation of metals in fish, it is important to consider parasites while interpreting bioaccumulation data from biomonitoring programmes. Accordingly, the first step is to take parasitism into consideration when simulating metal bioaccumulation in the fish host under laboratory conditions. In the present study, the accumulation of metals in fish-parasite systems was simulated by a one-compartment toxicokinetic model and compared to uninfected conspecifics. As such, metal accumulation in fish was assumed to result from a balance of different uptake and loss processes depending on the infection status. The uptake by parasites was considered an efflux from the fish host, similar to elimination. Physiological rate constants for the uninfected fish were parameterised based on the covalent index and the species weight while the parameterisation for the infected fish was carried out based on the reported effects of parasites on the uptake kinetics of the fish host. The model was then validated for the system of the chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis following 36-day exposure to waterborne Pb. The dissolved concentration of Pb in the exposure tank water fluctuated during the exposure, ranging from 40 to 120 μg/L. Generally, the present study shows that the one-compartment model can be an effective method for simulating the accumulation of metals in fish, taking into account effects of parasitism. In particular, the predicted concentrations of Cu, Fe, Zn, and Pb in the uninfected chub as well as in the infected chub and the acanthocephalans were within one order of magnitude of the measurements. The variation in the absorption efficiency and the elimination rate constant of the uninfected chub resulted in variations of about one order of magnitude in the predicted concentrations of Pb. Inclusion of further assumptions for simulating metal accumulation in the infected chub

  9. Development and Validation of a Biodynamic Model for Mechanistically Predicting Metal Accumulation in Fish-Parasite Systems

    PubMed Central

    Le, T. T. Yen; Nachev, Milen; Grabner, Daniel; Hendriks, A. Jan; Sures, Bernd

    2016-01-01

    Because of different reported effects of parasitism on the accumulation of metals in fish, it is important to consider parasites while interpreting bioaccumulation data from biomonitoring programmes. Accordingly, the first step is to take parasitism into consideration when simulating metal bioaccumulation in the fish host under laboratory conditions. In the present study, the accumulation of metals in fish-parasite systems was simulated by a one-compartment toxicokinetic model and compared to uninfected conspecifics. As such, metal accumulation in fish was assumed to result from a balance of different uptake and loss processes depending on the infection status. The uptake by parasites was considered an efflux from the fish host, similar to elimination. Physiological rate constants for the uninfected fish were parameterised based on the covalent index and the species weight while the parameterisation for the infected fish was carried out based on the reported effects of parasites on the uptake kinetics of the fish host. The model was then validated for the system of the chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis following 36-day exposure to waterborne Pb. The dissolved concentration of Pb in the exposure tank water fluctuated during the exposure, ranging from 40 to 120 μg/L. Generally, the present study shows that the one-compartment model can be an effective method for simulating the accumulation of metals in fish, taking into account effects of parasitism. In particular, the predicted concentrations of Cu, Fe, Zn, and Pb in the uninfected chub as well as in the infected chub and the acanthocephalans were within one order of magnitude of the measurements. The variation in the absorption efficiency and the elimination rate constant of the uninfected chub resulted in variations of about one order of magnitude in the predicted concentrations of Pb. Inclusion of further assumptions for simulating metal accumulation in the infected chub

  10. Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites.

    PubMed

    Augusto, Ronaldo de Carvalho; Tetreau, Guillaume; Chan, Philippe; Walet-Balieu, Marie-Laure; Mello-Silva, Clélia Christina; Santos, Claudia Portes; Grunau, Christoph

    2017-07-01

    Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts. We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics. We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without

  11. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system.

    PubMed

    van der Plaats, A; Maathuis, M H J; 'T Hart, N A; Bellekom, A A; Hofker, H S; van der Houwen, E B; Verkerke, G J; Leuvenink, H G D; Verdonck, P; Ploeg, R J; Rakhorst, G

    2006-12-01

    To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0-4 degrees C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO(2)) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0-4 degrees C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO(2) was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers. The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.

  12. Cardiac Involvement with Parasitic Infections

    PubMed Central

    Hidron, Alicia; Vogenthaler, Nicholas; Santos-Preciado, José I.; Rodriguez-Morales, Alfonso J.; Franco-Paredes, Carlos; Rassi, Anis

    2010-01-01

    Summary: Parasitic infections previously seen only in developing tropical settings can be currently diagnosed worldwide due to travel and population migration. Some parasites may directly or indirectly affect various anatomical structures of the heart, with infections manifested as myocarditis, pericarditis, pancarditis, or pulmonary hypertension. Thus, it has become quite relevant for clinicians in developed settings to consider parasitic infections in the differential diagnosis of myocardial and pericardial disease anywhere around the globe. Chagas' disease is by far the most important parasitic infection of the heart and one that it is currently considered a global parasitic infection due to the growing migration of populations from areas where these infections are highly endemic to settings where they are not endemic. Current advances in the treatment of African trypanosomiasis offer hope to prevent not only the neurological complications but also the frequently identified cardiac manifestations of this life-threatening parasitic infection. The lack of effective vaccines, optimal chemoprophylaxis, or evidence-based pharmacological therapies to control many of the parasitic diseases of the heart, in particular Chagas' disease, makes this disease one of the most important public health challenges of our time. PMID:20375355

  13. Interleukin 3 perfusion in W/Wv mice allows the development of macroscopic hematopoietic spleen colonies and restores cutaneous mast cell number

    SciTech Connect

    Ody, C.; Kindler, V.; Vassalli, P. )

    1990-07-01

    The genetically anemic W/Wv mice are characterized by the inability of their bone marrow cells to form macroscopic pluripotent hematopoietic colonies in the spleen of irradiated recipients upon transfer (colony-forming units). Furthermore, they almost totally lack mast cells, notably in the skin. In the present study, we have tested the effect of recombinant murine interleukin 3 (rmIL-3) on W/Wv mice hematopoiesis. Transfer of W/Wv bone marrow cells into lethally irradiated recipients perfused with rmIL-3 is followed by the appearance of macroscopic spleen colonies. Moreover, perfusion of rmIL-3 in W/Wv mice: (a) restores almost normal total numbers of hematopoietic precursors (colony-forming cells), but without modification of anemia; and (b) leads to the appearance of a normal number of mastocytes in the skin.

  14. In vitro activity of Peltophorum africanum Sond. (Fabaceae) extracts on the egg hatching and larval development of the parasitic nematode Trichostrongylus colubriformis.

    PubMed

    Bizimenyera, E S; Githiori, J B; Eloff, J N; Swan, G E

    2006-12-20

    Trichostrongylus colubriformis is an important cause of parasitic gastroenteritis in ruminants, where it causes protracted diarrhoea, rapid loss of weight, loss of production and death. The in vitro efficacy of extracts of Peltophorum africanum was determined against this parasitic nematode. Eggs and larvae of T. colubriformis were incubated at 23 degrees C in the extracts of the leaf, bark and root of P. africanum at concentrations of 0.008-25 mg ml-1 for 2 and 5 days, respectively. Thiabendazole and water were used as positive and negative controls, respectively. Inhibition of egg hatching and larval development increased significantly (P<0.05) with increasing concentrations of the extracts. Concentrations of 0.2-1.0 mg ml-1 of the extracts of leaf, stem bark, and root bark of P. africanum completely inhibited the hatching of eggs and development of larvae. No eggs and larvae of T. colubriformis could be observed in wells incubated with all the three extracts at concentrations of 5 and 25 mg ml-1. The in vitro model results support the traditional use of P. africanum against nematode parasites. Further research is required to isolate and structurally identify the active anthelmintic compounds, and to improve methods of plant extraction of the effective anthelmintic components that will be readily adaptable for use by rural communities against helminthosis.

  15. Effects of Lobesia botrana (Lepidoptera: Tortricidae) egg age, density, and UV treatment on parasitism and development of Trichogramma cacoeciae (Hymenoptera: Trichogrammatidae).

    PubMed

    Moreno, Fernando; Pérez-Moreno, Ignacio; Marco, Vicente

    2009-10-01

    Integrated pest management (IPM) supports the integration of all rational control methods available. Biological control is one of those control methods. Thus, the influence of Lobesia botrana Den. and Schiff. egg age, density, and sterilization by UV light on parasitism and progeny development of a Trichogramma cacoeciae Marchal strain from La Rioja, Spain, was studied. Understanding this influence is important for the development of biological control programs. UV-killed eggs are widely used for mass rearing Trichogramma. Trichogramma cacoeciae preferred young eggs (0-72 h old), and the largest number of progeny were produced from these eggs, especially from 48- to 72-h-old eggs. The relationship between the number of eggs parasitized by T. cacoeciae and its density (within the range studied) was linear (R (2) adjusted = 0.93), with constant values (72.2-93.7%) for discovery rate (an estimator of searching capacity). UV treatment did not affect the number of progeny produced or parasitism tendency and was thus a helpful tool for the mass-rearing process. Based on its response to egg age and density, our T. cacoeciae strain showed potential for control of L. botrana.

  16. Effect of anti-mosquito midgut antibodies on development of malaria parasite, Plasmodium vivax and fecundity in vector mosquito Anopheles culicifacies (Diptera: culicidae).

    PubMed

    Chugh, Manoj; Adak, T; Sehrawat, Neelam; Gakhar, S K

    2011-04-01

    The effect of anti-mosquito-midgut antibodies on the development of the malaria parasite, P. vivax was studied by feeding the vector mosquito, An. culicifacies with infected blood supplemented with serum from immunized rabbits. In order to get antisera, rabbits were immunized with midgut proteins of three siblings species of Anopheles culicifacies, reported to exhibit differential vectorial capacity. The mosquitoes that ingested anti-midgut antibodies along with infectious parasites had significantly fewer oocysts compared to the control group of mosquitoes. The immunized rabbits generated high titer of antibodies. Their cross reactivity amongst various tissues of the same species and with other sibling species was also determined. Immunogenic polypeptides expressed in the midgut of glucose or blood fed An. culicifacies sibling species were identified by Western blotting. One immunogenic polypeptide of 62 kDa was exclusively present in the midgut of species A. Similarly, three polypeptides of 97, 94 and 58 kDa and one polypeptide of 23 kDa were present exclusively in species B and C respectively. Immunoelectron microscopy revealed the localization of these antigens on baso-lateral membrane and microvilli. The effects of anti-mosquito midgut antibodies on fecundity, longevity, mortality and engorgement of mosquitoes were studied. Fecundity was also reduced significantly. These observations open an avenue for research toward the development of a vector-based malaria parasite transmission-blocking vaccine.

  17. Perfusion Bioreactor Module

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1990-01-01

    Perfusion bioreactor module, self-contained, closed-loop cell-culture system that operates in microgravity or on Earth. Equipment supports growth or long-term maintenance of cultures of human or other fragile cells for experiments in basic cell biology or process technology. Designed to support proliferation (initially at exponential rates of growth) of cells in complex growth medium and to maintain confluent cells in defined medium under conditions optimized to permit or encourage selected functions of cells, including secretion of products of cells into medium.

  18. Glomerulopathy Associated with Parasitic Infections

    PubMed Central

    van Velthuysen, M.-L. F.; Florquin, S.

    2000-01-01

    Although parasitic infections do not usually present with disturbance in renal function, glomerular lesions can be seen in most of these infections. The glomerular lesions observed in parasitic infections cover the whole range of glomerular lesions known, but most of them are proliferative. Little is known of the exact pathogenic mechanisms. In this review, we try to explain the glomerular lesions associated with parasitic infections in terms of the specific immunologic events observed during these diseases against the background of recent developments in the general knowledge of the pathogenesis of glomerular disease. PMID:10627491

  19. A secretory multifunctional serine protease, DegP of Plasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development.

    PubMed

    Sharma, Shweta; Jadli, Mohit; Singh, Anu; Arora, Kavita; Malhotra, Pawan

    2014-03-01

    Plasmodium falciparum heat shock proteins and proteases are known for their indispensable roles in parasite virulence and survival in the host cell. They neutralize various host-derived stress responses that are deleterious for parasite growth and invasion. We report identification and functional characterization of the first DegP from an apicomplexan (P. falciparum). To determine the molecular identity and functions of the parasite-encoded DegP, we complemented the Escherichia coli degP null mutant with a putative PfdegP gene, and the results showed that PfDegP complements the growth defect of the temperature sensitive DegP-deficient mutant and imparts resistance to non-permissive temperatures and oxidative stress. Molecular interaction studies showed that PfDegP exists as a complex with parasite-encoded heat shock protein 70, iron superoxide dismutase and enolase. DegP expression is significantly induced in parasite culture upon heat shock/oxidative stress. Our data suggest that the PfDegP protein may play a role in the growth and development of P. falciparum through its ability to confer protection against thermal/oxidative stress. Antibody against DegP showed anti-plasmodial activity against blood-stage parasites in vitro, suggesting that PfDegP and its associated complex may be a potential focus for new anti-malarial therapies. ●PfDegP physically interacts with PfHsp70 and PfEno by anti-bait co-immunoprecipitation (View interaction) ●PfDegP physically interacts with PfEno, PfSod, PfOat, PfHsp70, PfLDH and PfGpi by anti-bait co-immunoprecipitation (View interaction) ●PfHsp-70 and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP physically interacts with PfOat, PfHsp70, PfEno, PfSod, PfGpi and PfLDH by surface plasmon resonance (View interaction) ●PfEno and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP and PfHsp70 co-localize by co-sedimentation through density gradient (View interaction). © 2014

  20. Development and validation of an automatic method to detect the latest contracting viable left ventricular segments to assist guide CRT therapy from gated SPECT myocardial perfusion imaging.

    PubMed

    Zhou, Weihua; Tao, Ningchao; Hou, Xiaofeng; Wang, Yao; Folks, Russell D; Cooke, David C; Moncayo, Valeria M; Garcia, Ernest V; Zou, Jiangang

    2017-03-28

    The purpose of this study is to use ECG-gated SPECT MPI to detect the latest contracting viable left ventricular (LV) segments to help guide the LV probe placement used in CRT therapy and to validate segment selection against the visual integration method by experts. For each patient, the resting ECG-gated SPECT MPI short-axis images were sampled in 3D to generate a polar map of the perfusion distribution used to determine LV myocardial viability, and to measure LV synchronicity using our phase analysis tool. In the visual integration method, two experts visually interpreted the LV viability and mechanical dyssynchrony from the short-axis images and polar maps of viability and phase, to determine the latest contracting viable segments using the 17-segment model. In the automatic method, the apical segments, septal segments, and segments with more than 50% scar were excluded as these are not candidates for CRT LV probe placement. Amongst the remaining viable segments, the segments, whose phase angles were within 10° of the latest phase angle (the most delayed contracting segment), were identified for potential CRT LV probe placement and ranked based on the phase angles of the segments. Both methods were tested in 36 pre-CRT patients who underwent ECG-gated SPECT MPI. The accuracy was determined as the percent agreement between the visual integration and automatic methods. The automatic method was performed by a second independent operator to evaluate the inter-operator processing reproducibility. In all the 36 patients, the LV lead positions of the 1st choices recommended by the automatic and visual integration methods were in the same segments in 35 patients, which achieved an agreement rate of 97.2%. In the inter-operator reproducibility test, the LV lead positions of the 1st choices recommended by the two operators were in the same segments in 25 patients, and were in the adjacent segments in 7 patients, which achieved an overall agreement of 88.8%. An automatic

  1. Asynchronicity of facial blood perfusion in migraine.

    PubMed

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A; Kamshilin, Alexei A; Närhi, Matti; Karjalainen, Pasi A; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

  2. Asynchronicity of Facial Blood Perfusion in Migraine

    PubMed Central

    Zaproudina, Nina; Teplov, Victor; Nippolainen, Ervin; Lipponen, Jukka A.; Kamshilin, Alexei A.; Närhi, Matti; Karjalainen, Pasi A.; Giniatullin, Rashid

    2013-01-01

    Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology. PMID:24324592

  3. Protozoan Parasites.

    PubMed

    Custodio, Haidee

    2016-02-01

    • Stool antigen detection for Cryptosporidium sp, Giardia lamblia and Entamoeba histolytica are now commercially available, have better sensitivity and specificity than the traditional stool microscopy, and are less dependent on personnel skill. Tests employing newer techniques with faster turnaround time are also available for diagnosing trichomoniasis.• Nitazoxanide, the only U.S. Food and Drug Administration-approved medication for therapy of cryptosporidiosis, is effective among immunocompetent patients. However, on the basis of strong evidence from multiple clinical trials, nitazoxanide is considered ineffective among immunocompromised patients. (14) • Giardiasis can be asymptomatic or have a chronic course leading to malabsorption and failure to thrive. It can be treated with metronidazole, tinidazole, or nitazoxanide. On the basis of growing observational studies, postinfectious and extraintestinal manifestations of giardiasis occur, but the mechanisms are unclear. Given the high prevalence of giardiasis, public health implications need to be defined. (16) • Eradicating E histolytica from the gastrointestinal tract requires only intraluminal agent therapy. Therapy for invasive illnesses requires use of imidazole followed by intraluminal agents to eliminate persistent intraluminal parasites. • Malaria is considered the most lethal parasitic infection, with Plasmodium falciparum as the predominant cause of mortality. P vivax and P ovale can be dormant in the liver, and primaquine is necessary to resolve infection by P vivax and P ovale. • Among immunocompetent patients, infection with Toxoplasma gondii may be asymptomatic, involve localized lymphadenopathy, or cause ocular infection. In immunocompromised patients, reactivation or severe infection is not uncommon. On the basis of limited observational studies (there are no well-controlled randomized trials), therapy is recommended for acute infection during pregnancy to prevent transmission to the

  4. Parasites in algae mass culture.

    PubMed

    Carney, Laura T; Lane, Todd W

    2014-01-01

    Parasites are now known to be ubiquitous across biological systems and can play an important role in modulating algal populations. However, there is a lack of extensive information on their role in artificial ecosystems such as algal production ponds and photobioreactors. Parasites have been implicated in the demise of algal blooms. Because individual mass culture systems often tend to be unialgal and a select few algal species are in wide scale application, there is an increased potential for parasites to have a devastating effect on commercial scale monoculture. As commercial algal production continues to expand with a widening variety of applications, including biofuel, food and pharmaceuticals, the parasites associated with algae will become of greater interest and potential economic impact. A number of important algal parasites have been identified in algal mass culture systems in the last few years and this number is sure to grow as the number of commercial algae ventures increases. Here, we review the research that has identified and characterized parasites infecting mass cultivated algae, the techniques being proposed and or developed to control them, and the potential impact of parasites on the future of the algal biomass industry.

  5. Parasites in algae mass culture

    PubMed Central

    Carney, Laura T.; Lane, Todd W.

    2014-01-01

    Parasites are now known to be ubiquitous across biological systems and can play an important role in modulating algal populations. However, there is a lack of extensive information on their role in artificial ecosystems such as algal production ponds and photobioreactors. Parasites have been implicated in the demise of algal blooms. Because individual mass culture systems often tend to be unialgal and a select few algal species are in wide scale application, there is an increased potential for parasites to have a devastating effect on commercial scale monoculture. As commercial algal production continues to expand with a widening variety of applications, including biofuel, food and pharmaceuticals, the parasites associated with algae will become of greater interest and potential economic impact. A number of important algal parasites have been identified in algal mass culture systems in the last few years and this number is sure to grow as the number of commercial algae ventures increases. Here, we review the research that has identified and characterized parasites infecting mass cultivated algae, the techniques being proposed and or developed to control them, and the potential impact of parasites on the future of the algal biomass industry. PMID:24936200

  6. Pregnancy, nutrition and parasitic diseases.

    PubMed

    Steketee, Richard W

    2003-05-01

    In the developing world, young women, pregnant women, and their infants and children frequently experience a cycle where undernutrition (macronutrient and micronutrient) and repeated infection, including parasitic infections, lead to adverse consequences that can continue from one generation to the next. Among parasitic infections, malaria and intestinal helminths coexist widely with micronutrient deficiencies and contribute importantly to anemia and this cycle of retarded growth and development. In somewhat more limited or focal geographic settings, other parasitic diseases (e.g., schistosomiasis, filariasis) contribute similarly to this cycle. It is undoubtedly much better to enter a pregnancy free of infection and nutritionally replete than the various alternatives. Existing intervention strategies for micronutrient support and for the control of common parasitic infections before or during pregnancy, particularly malaria and intestinal helminths, should be followed. However, further research to identify barriers and priority approaches to achieving this goal remain very important in resource-poor settings where targeted public health efforts are required.

  7. Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound

    PubMed Central

    Portes, J. A.; Souza, T. G.; dos Santos, T. A. T.; da Silva, L. L. R.; Ribeiro, T. P.; Pereira, M. D.; Horn, A.; Fernandes, C.; DaMatta, R. A.; de Souza, W.

    2015-01-01

    Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPCINOL)(SO4)]2-μ-oxo, in which HPCINOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on T. gondii infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations of up to 200 μM but was very active against the parasite, with a 50% inhibitory concentration (IC50) of 3.6 μM after 48 h of treatment. Cyst formation was observed after treatment, as indicated by the appearance of a cyst wall, Dolichos biflorus lectin staining, and scanning and transmission electron microscopy characteristics. Ultrastructural changes were also seen in T. gondii, including membrane blebs and clefts in the cytoplasm, with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of T. gondii, inducing cystogenesis and parasite death. PMID:26392498

  8. Reduction of Toxoplasma gondii Development Due to Inhibition of Parasite Antioxidant Enzymes by a Dinuclear Iron(III) Compound.

    PubMed

    Portes, J A; Souza, T G; dos Santos, T A T; da Silva, L L R; Ribeiro, T P; Pereira, M D; Horn, A; Fernandes, C; DaMatta, R A; de Souza, W; Seabra, S H

    2015-12-01

    Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan that can infect a wide range of vertebrate cells. Here, we describe the cytotoxic effects of the dinuclear iron compound [Fe(HPCINOL)(SO4)]2-μ-oxo, in which HPCINOL is the ligand 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, on T. gondii infecting LLC-MK2 host cells. This compound was not toxic to LLC-MK2 cells at concentrations of up to 200 μM but was very active against the parasite, with a 50% inhibitory concentration (IC50) of 3.6 μM after 48 h of treatment. Cyst formation was observed after treatment, as indicated by the appearance of a cyst wall, Dolichos biflorus lectin staining, and scanning and transmission electron microscopy characteristics. Ultrastructural changes were also seen in T. gondii, including membrane blebs and clefts in the cytoplasm, with inclusions similar to amylopectin granules, which are typically found in bradyzoites. An analysis of the cell death pathways in the parasite revealed that the compound caused a combination of apoptosis and autophagy. Fluorescence assays demonstrated that the redox environment in the LLC-MK2 cells becomes oxidant in the presence of the iron compound. Furthermore, a reduction in superoxide dismutase and catalase activities in the treated parasites and the presence of reactive oxygen species within the parasitophorous vacuoles were observed, indicating an impaired protozoan response against these radicals. These findings suggest that this compound disturbs the redox equilibrium of T. gondii, inducing cystogenesis and parasite death.

  9. Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases

    PubMed Central

    Schad, Caroline; Baum, Ulrike; Frank, Benjamin; Dietzel, Uwe; Mattern, Felix; Gomes, Carlos; Ponte-Sucre, Alicia; Moll, Heidrun

    2015-01-01

    Leishmaniasis is one of the major neglected tropical diseases of the world. Druggable targets are the parasite cysteine proteases (CPs) of clan CA, family C1 (CAC1). In previous studies, we identified two peptidomimetic compounds, the aziridine-2,3-dicarboxylate compounds 13b and 13e, in a series of inhibitors of the cathepsin L (CL) subfamily of the papain clan CAC1. Both displayed antileishmanial activity in vitro while not showing cytotoxicity against host cells. In further investigations, the mode of action was characterized in Leishmania major. It was demonstrated that aziridines 13b and 13e mainly inhibited the parasitic cathepsin B (CB)-like CPC enzyme and, additionally, mammalian CL. Although these compounds induced cell death of Leishmania promastigotes and amastigotes in vitro, the induction of a proleishmanial T helper type 2 (Th2) response caused by host CL inhibition was observed in vivo. Therefore, we describe here the synthesis of a new library of more selective peptidomimetic aziridine-2,3-dicarboxylates discriminating between host and parasite CPs. The new compounds are based on 13b and 13e as lead structures. One of the most promising compounds of this series is compound s9, showing selective inhibition of the parasite CPs LmaCatB (a CB-like enzyme of L. major; also named L. major CPC) and LmCPB2.8 (a CL-like enzyme of Leishmania mexicana) while not affecting mammalian CL and CB. It displayed excellent leishmanicidal activities against L. major promastigotes (50% inhibitory concentration [IC50] = 37.4 μM) and amastigotes (IC50 = 2.3 μM). In summary, we demonstrate a new selective aziridine-2,3-dicarboxylate, compound s9, which might be a good candidate for future in vivo studies. PMID:26596939

  10. Development and evaluation of a real-time PCR assay for detection and quantification of blastocystis parasites in human stool samples: prospective study of patients with hematological malignancies.

    PubMed

    Poirier, Philippe; Wawrzyniak, Ivan; Albert, Aurélie; El Alaoui, Hicham; Delbac, Frédéric; Livrelli, Valérie

    2011-03-01

    Blastocystis anaerobic parasites are widespread worldwide in the digestive tract of many animal species, including humans. Epidemiological Blastocystis studies are often limited by the poor sensitivity of standard parasitological assays for its detection. This report presents a highly sensitive real-time quantitative PCR (qPCR) assay developed to detect Blastocystis parasites in stool samples. The assay targets a partial sequence of the Blastocystis small ribosomal subunit (SSU) rRNA gene, allowing subtyping (ST) of Blastocystis isolates by direct sequencing of qPCR products. This qPCR method was assessed in a prospective study of 186 patients belonging to two cohorts--a group of 94 immunocompromised patients presenting hematological malignancies and a control group of 92 nonimmunocompromised patients. Direct-light microscopy and xenic in vitro stool culture analysis showed only 29% and 52% sensitivity, respectively, compared to our qPCR assay. Of the 27 (14.5%) Blastocystis-positive patients, 8 (4%) experienced digestive symptoms. No correlation was found between symptomatic patients and immune status, parasite load, or parasite subtypes, although subtyping of all isolates revealed a high (63.0%) prevalence of ST4. Two unexpected avian subtypes were found, i.e., ST6 and ST7, which are frequently isolated in Asia but rarely present in Western countries. In conclusion, this qPCR proved by far the most sensitive of the tested methods and allowed subtype determination by direct sequencing of qPCR products. New diagnostic tools such as the qPCR are essential for evaluating the clinical relevance of Blastocystis subtypes and their role in acute or chronic digestive disorders.

  11. Extensive lysine acetylation occurs in evolutionarily conserved metabolic pathways and parasite-specific functions during Plasmodium falciparum intraerythrocytic development

    PubMed Central

    Miao, Jun; Lawrence, Matthew; Jeffers, Victoria; Zhao, Fangqing; Parker, Daniel; Ge, Ying; Sullivan, William J.; Cui, Liwang

    2013-01-01

    Summary Lysine acetylation has emerged as a major posttranslational modification involved in diverse cellular functions. Using a combination of immunoisolation and liquid chromatography coupled to accurate mass spectrometry, we determined the first acetylome of the human malaria parasite Plasmodium falciparum during its active proliferation in erythrocytes with 421 acetylation sites identified in 230 proteins. Lysine-acetylated proteins are distributed in the nucleus, cytoplasm, mitochondrion, and apicoplast. Whereas occurrence of lysine acetylation in a similarly wide range of cellular functions suggests conservation of lysine acetylation through evolution, the Plasmodium acetylome also revealed significant divergence from those of other eukaryotes and even the closely-related parasite Toxoplasma. This divergence is reflected in the acetylation of a large number of Plasmodium-specific proteins and different acetylation sites in evolutionarily conserved acetylated proteins. A prominent example is the abundant acetylation of proteins in the glycolysis pathway but relatively deficient acetylation of enzymes in the citrate cycle. Using specific transgenic lines and inhibitors, we determined that the acetyltransferase PfMYST and lysine deacetylases play important roles in regulating the dynamics of cytoplasmic protein acetylation. The Plasmodium acetylome provides an exciting start point for further exploration of functions of acetylation in the biology of malaria parasites. PMID:23796209

  12. Extensive lysine acetylation occurs in evolutionarily conserved metabolic pathways and parasite-specific functions during Plasmodium falciparum intraerythrocytic development.

    PubMed

    Miao, Jun; Lawrence, Matthew; Jeffers, Victoria; Zhao, Fangqing; Parker, Daniel; Ge, Ying; Sullivan, William J; Cui, Liwang

    2013-08-01

    Lysine acetylation has emerged as a major post-translational modification involved in diverse cellular functions. Using a combination of immunoisolation and liquid chromatography coupled to accurate mass spectrometry, we determined the first acetylome of the human malaria parasite Plasmodium falciparum during its active proliferation in erythrocytes with 421 acetylation sites identified in 230 proteins. Lysine-acetylated proteins are distributed in the nucleus, cytoplasm, mitochondrion and apicoplast. Whereas occurrence of lysine acetylation in a similarly wide range of cellular functions suggests conservation of lysine acetylation through evolution, the Plasmodium acetylome also revealed significant divergence from those of other eukaryotes and even the closely related parasite Toxoplasma. This divergence is reflected in the acetylation of a large number of Plasmodium-specific proteins and different acetylation sites in evolutionarily conserved acetylated proteins. A prominent example is the abundant acetylation of proteins in the glycolysis pathway but relatively deficient acetylation of enzymes in the citrate cycle. Using specific transgenic lines and inhibitors, we determined that the acetyltransferase PfMYST and lysine deacetylases play important roles in regulating the dynamics of cytoplasmic protein acetylation. The Plasmodium acetylome provides an exciting start point for further exploration of functions of acetylation in the biology of malaria parasites. © 2013 John Wiley & Sons Ltd.

  13. Harmonic analysis of perfusion pumps.

    PubMed

    Dougherty, F Carroll; Donovan, F M; Townsley, Mary I

    2003-12-01

    The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.

  14. Molecular diagnostics and parasitic disease.

    PubMed

    Vasoo, Shawn; Pritt, Bobbi S

    2013-09-01

    Molecular parasitology represents an emerging field in microbiology diagnostics. Although most assays use nonstandardized, laboratory-developed methods, a few commercial systems have recently become available and are slowly being introduced into larger laboratories. In addition, a few methodologies show promise for use in field settings in which parasitic infections are endemic. This article reviews the available techniques and their applications to major parasitic diseases such as malaria, leishmaniasis, and trichomoniasis.

  15. Congenital parasitic infections: a review.

    PubMed

    Carlier, Yves; Truyens, Carine; Deloron, Philippe; Peyron, François

    2012-02-01

    This review defines the concepts of maternal-fetal (congenital) and vertical transmissions (mother-to-child) of pathogens and specifies the human parasites susceptible to be congenitally transferred. It highlights the epidemiological features of this transmission mode for the three main congenital parasitic infections due to Toxoplasma gondii, Trypanosoma cruzi and Plasmodium sp. Information on the possible maternal-fetal routes of transmission, the placental responses to infection and timing of parasite transmission are synthesized and compared. The factors susceptible to be involved in parasite transmission and development of congenital parasitic diseases, such as the parasite genotypes, the maternal co-infections and parasitic load, the immunological features of pregnant women and the capacity of some fetuses/neonates to overcome their immunological immaturity to mount an immune response against the transmitted parasites are also discussed and compared. Analysis of clinical data indicates that parasitic congenital infections are often asymptomatic, whereas symptomatic newborns generally display non-specific symptoms. The long-term consequences of congenital infections are also mentioned, such as the imprinting of neonatal immune system and the possible trans-generational transmission. The detection of infection in pregnant women is mainly based on standard serological or parasitological investigations. Amniocentesis and cordocentesis can be used for the detection of some fetal infections. The neonatal infection can be assessed using parasitological, molecular or immunological methods; the place of PCR in such neonatal diagnosis is discussed. When such laboratory diagnosis is not possible at birth or in the first weeks of life, standard serological investigations can also be performed 8-10 months after birth, to avoid detection of maternal transmitted antibodies. The specific aspects of treatment of T. gondii, T. cruzi and Plasmodium congenital infections are

  16. Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators: effect on erythrocyte membrane integrity, parasite development and the intracellular labile iron pool.

    PubMed

    Walcourt, Asikiya; Kurantsin-Mills, Joseph; Kwagyan, John; Adenuga, Babafemi B; Kalinowski, Danuta S; Lovejoy, David B; Lane, Darius J R; Richardson, Des R

    2013-12-01

    Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum, in culture and in animal and human studies. We previously reported the anti-plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In fact, these ligands showed greater growth inhibition of chloroquine-sensitive (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture compared to desferrioxamine (DFO). The present study examined the effects of 311, N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development. While the characteristic biconcave disk shape of the erythrocytes was unaffected, the chelators caused very slight hemolysis at IC50 values that inhibited parasite growth. The chelators 311, N4mT and N4pT affected all stages of the intra-erythrocytic development cycle (IDC) of P. falciparum in culture. However, while these ligands primarily affected the ring-stage, DFO inhibited primarily trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC were inhibited by significantly lower concentrations of 311, N4mT, and N4pT (IC50=4.45±1.70, 10.30±4.40, and 3.64±2.00μM, respectively) than DFO (IC50=23.43±3.40μM). Complexation of 311, N4mT and N4pT with iron reduced their anti-plasmodial activity. Estimation of the intracellular labile iron pool (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT corresponded to their anti-plasmodial activities, suggesting that the LIP may be a potential source of non-heme iron for parasite metabolism within the erythrocyte. This study has implications for malaria chemotherapy that specifically disrupts parasite iron utilization.

  17. Experimental study on the segmental perfusion and preservation of spleen.

    PubMed

    Limin, H; Hongchi, J; Wenjie, D; Haiquan, Q; Jun, X

    1999-12-01

    Spleen transplanlation has developed to be an effective strategy for hemophilia A. But it has not been reported up to date that which kind of established solutions is most suitable for perfusion and preservation of spleen. This study aimed to establish some experiences with the comparison among Hartmann's solution, Collins' solution and WMO-I solution, in order to instruct the clinical spleen transplantation. After the splenic artery and vein were dissociated clearly, three kinds of perfusion solutions began to perfuse the corresponding segments of spleen with a randomized sequence. When the efferent fluids from the splenic vein became clear, the perfused spleen segments were preserved for different durations with the same perfusing solution to calculate the survival rate of splencocyte (SRS) and were examined with light and electron microscopy. Among the three solutions, SRS with WMO-I solution was significantly higher than those of the other two (P<0.001). The perfused spleen with WMO-I solution showed the slightest morphological changes and a significant longer preservation duration than those with the other two (P<0.05 or P<0.01). Among the three solutions, WMO-I solution was most suitable for perfusion and preservation of spleen.

  18. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  19. Double impact: natural molluscicide for schistosomiasis vector control also impedes development of Schistosoma mansoni cercariae into adult parasites

    PubMed Central

    Tetreau, Guillaume; Chan, Philippe; Walet-Balieu, Marie-Laure; Mello-Silva, Clélia Christina; Santos, Claudia Portes; Grunau, Christoph

    2017-01-01

    Background Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite’s biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite’s life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts. Methodology/Principal findings We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics. Conclusions/Significance We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with

  20. Influence of the gestational stage on the clinical course, lesional development and parasite distribution in experimental ovine neosporosis.

    PubMed

    Arranz-Solís, David; Benavides, Julio; Regidor-Cerrillo, Javier; Fuertes, Miguel; Ferre, Ignacio; Ferreras, Maria Del Carmen; Collantes-Fernández, Esther; Hemphill, Andrew; Pérez, Valentín; Ortega-Mora, Luis Miguel

    2015-03-03

    Neospora caninum is considered one of the main causes of abortion in cattle, yet recent studies have also emphasised its relevance as an abortifacient in small ruminants. In order to gain deeper insight into the pathogenesis of ovine neosporosis, pregnant ewes were intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at days 40, 90 or 120 of gestation. Infection during the first term resulted in the death of all foetuses between days 19 and 21 post-infection, showing mainly necrotic lesions in foetal liver and the highest parasite DNA detection and burden in both placenta and foetal viscera. After infection at day 90, foetal death was also detected in all ewes, although later (34-48 days post-infection). In this group, lesions were mainly inflammatory. Foetal livers showed the lowest frequency of lesions, as well as the lowest parasite detection and burden. All ewes infected at day 120 delivered viable lambs, although 3 out of 9 showed weakness and recumbency. Neospora DNA was detected in all lambs but one, and parasite burden was similar to that observed in day 90 group. Lesions in this group showed more conspicuous infiltration of inflammatory cells and higher frequency in foetal brain and muscle when compared to both previous groups. These results highlight the crucial role that the stage of gestation plays on the course of ovine neosporosis, similar to that reported in bovine neosporosis, and open the doors to consider sheep as a valid model for exogenous transplacental transmission for ruminant neosporosis.

  1. Serodiagnosis of parasitic diseases.

    PubMed Central

    Maddison, S E

    1991-01-01

    In this review on serodiagnosis of parasitic diseases, antibody detection, antigen detection, use of monoclonal antibodies in parasitic serodiagnosis, molecular biological technology, and skin tests are discussed. The focus at the Centers for Disease Control on developing improved antigens, a truly quantitative FAST-enzyme-linked immunosorbent assay, and the very specific immunoblot assays for antibody detection is highlighted. The last two assays are suitable for field studies. Identification of patient response in terms of immunoglobulin class or immunoglobulin G subclass isotypes or both is discussed. Immunoglobulin isotypes may asist in defining the stage of some diseases. In other instances, use of a particular anti-isotype conjugate may increase the specificity of the assay. Monoclonal antibodies have played important roles in antigen purification and identification, in competitive antibody assays with increased sensitivity and specificity, and in assays for antigen detection in serum, body fluids, or excreta. Molecular biological technology has allowed significant advances in the production of defined parasitic serodiagnostic antigens. PMID:1747862

  2. Parasitic Myoma After Morcellation

    PubMed Central

    Sinha, Rakesh; Sundaram, Meenakshi; Lakhotia, Smita; Kadam, Pratima; Rao, Gayatri; Mahajan, Chaitali

    2009-01-01

    We report an interesting case of parasitic fibroid which developed from a morcellation remnant following laparoscopic myomectomy. The patient presented with incidental finding of pelvic mass in 2005. She underwent laparoscopic myomectomy for a myoma extending from the Pouch of Douglas to both sides of broad ligament. She subsequently presented with abdominal pain 3 years later in 2008. She underwent total laparoscopic hysterectomy with removal of broad ligament fibroids. During her hysterectomy, a right lumbar mass attached to the omentum was detected, which was excised laparoscopically. Histopathology of the mass confirmed it to be consistent with leiomyoma. This mass could probably be a morcellation remnant that has grown to this size taking blood supply from the omentum. We report this case to emphasize that all tissue pieces that are morcellated should be diligently removed. Even small bits displaced into the upper abdomen can result in parasitic fibroids. Thus, it can be concluded that parasitic myomas can arise from morcellated remnants and grow depending on the blood supply. PMID:22442523

  3. Perfusion Electronic Record Documentation Using Epic Systems Software.

    PubMed

    Steffens, Thomas G; Gunser, John M; Saviello, George M

    2015-12-01

    This paper describes the design and use of Epic Systems software for documentation of perfusion activities as part of the patient electronic medical record. The University of Wisconsin Hospital and Clinics adapted the Anesthesia software module and developed an integrated perfusion/anesthesia record for the documentation of cardiac and non-cardiac surgical procedures. This project involved multiple committees, approvals, and training to successfully implement. This article will describe our documentation options, concepts, design, challenges, training, and implementation during our initial experience.

  4. Development and availability of the free-living stages of Ostertagia gruehneri, an abomasal parasite of barrenground caribou (Rangifer tarandus groenlandicus), on the Canadian tundra.

    PubMed

    Hoar, Bryanne M; Ruckstuhl, Kathreen; Kutz, Susan

    2012-07-01

    Climate change in the Arctic is anticipated to alter the ecology of northern ecosystems, including the transmission dynamics of many parasite species. One parasite of concern is Ostertagia gruehneri, an abomasal nematode of Rangifer ssp. that causes reduced food intake, weight loss, and decreased pregnancy rates in reindeer. We investigated the development, availability, and overwinter survival of the free-living stages of O. gruehneri on the tundra. Fecal plots containing O. gruehneri eggs were established in the Northwest Territories, Canada under natural and artificially warmed conditions and sampled throughout the growing season of 2008 and the spring of 2009. Infective L3 were present 3-4 weeks post-establishment from all trials under both treatments, except for the trial established 4 July 2008 under warmed conditions wherein the first L3 was recovered 7 weeks post-establishment. These plots were exposed to significantly more time above 30°C than the natural plots established on the same date, suggesting a maximum temperature threshold for development. There was high overwinter survival of L2 and L3 across treatments and overwintering L2 appeared to develop to L3 the following spring. The impact of climate change on O. gruehneri is expected to be dynamic throughout the year with extreme maximum temperatures negatively impacting development rates.

  5. Perfusion measurement in acute pancreatitis using dynamic perfusion MDCT.

    PubMed

    Bize, Pierre E; Platon, Alexandra; Becker, Christoph D; Poletti, Pierre-Alexandre

    2006-01-01

    Our objective was to determine whether MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis in the initial phase of the disease. One hundred six patients with abdominal pain were prospectively enrolled in this study. Patients were separated into two groups: P1 (severe) and P2 (mild) acute pancreatitis. Mean perfusion value was 24.8 mL/100 mL/min in the P1 group and 50.5 mL/100 mL/min in the P2 group (p = 0.0016, significant). Our preliminary data suggest that pancreatic perfusion measurement using MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis.

  6. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

    compared to the 0.5g curve) fall in flow. Fig. 9b, showing the 5g case, strongly suggests a possible, so-called, " luxury perfusion ", in which natural...as the luxury perfusion situation which bypasses the flow with the nutrients it carries (through newly opened collaterals) and result in a "blackout...89-0054 CEREBRAL-BODY PERFUSION MODEL S. Sorek’, J. Bear2, and M., Feinsod3 in Collaboration with K. Allen4, L. Bunt5 and S. Ben-IHaiM6 July 1990

  7. Creation of an ensemble of simulated cardiac cases and a human observer study: tools for the development of numerical observers for SPECT myocardial perfusion imaging

    NASA Astrophysics Data System (ADS)

    O'Connor, J. Michael; Pretorius, P. Hendrik; Gifford, Howard C.; Licho, Robert; Joffe, Samuel; McGuiness, Matthew; Mehurg, Shannon; Zacharias, Michael; Brankov, Jovan G.

    2012-02-01

    Our previous Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI) research explored the utility of numerical observers. We recently created two hundred and eighty simulated SPECT cardiac cases using Dynamic MCAT (DMCAT) and SIMIND Monte Carlo tools. All simulated cases were then processed with two reconstruction methods: iterative ordered subset expectation maximization (OSEM) and filtered back-projection (FBP). Observer study sets were assembled for both OSEM and FBP methods. Five physicians performed an observer study on one hundred and seventy-nine images from the simulated cases. The observer task was to indicate detection of any myocardial perfusion defect using the American Society of Nuclear Cardiology (ASNC) 17-segment cardiac model and the ASNC five-scale rating guidelines. Human observer Receiver Operating Characteristic (ROC) studies established the guidelines for the subsequent evaluation of numerical model observer (NO) performance. Several NOs were formulated and their performance was compared with the human observer performance. One type of NO was based on evaluation of a cardiac polar map that had been pre-processed using a gradient-magnitude watershed segmentation algorithm. The second type of NO was also based on analysis of a cardiac polar map but with use of a priori calculated average image derived from an ensemble of normal cases.

  8. Emergence trap developed to capture adult large pine weevil Hylobius abietis (Coleoptera: Curculionidae) and its parasite Bracon hylobii (Hymenoptera: Braconidae).

    PubMed

    Moore, R

    2001-04-01

    A novel type of emergence trap capable of capturing and separating 'live' insect catches is described. The trap was shown to be 96% efficient at capturing newly emergent adult Hylobius abietis Linnaeus on bare ground and at least 82% efficient over stumps on a weedy Sitka spruce clearfell. The trap was more than 80% efficient at capturing Bracon hylobii Ratzeburg, the most commonly found parasite of H. abietis. It was also shown to be effective at capturing adult H. abietis of unknown age (98%), indicating that it could also be used to trap out H. abietis from known areas to estimate on-site overwintering densities. Fifty-four percent of newly emergent weevils were captured within 12 h of release on bare mineral soils. Forty-two percent of unknown age weevils and 52% of parasites were captured within 1 h of their release within the trap. The rapid rates of capture mean that when traps are checked frequently they can be used to reflect accurately temporal patterns of emergence. Its potential for use in control programmes and ecological studies is discussed.

  9. Distributed Perfusion Educational Model: A Shift in Perfusion Economic Realities

    PubMed Central

    Austin, Jon W.; Evans, Edward L.; Hoerr, Harry R.

    2005-01-01

    Abstract: In recent years, a steady decline in the number of perfusion education programs in the United States has been noted. At the same time, there has been a parallel decline in the number of students graduated from perfusion educational programs in the United States. Also, as noted by several authors, there has been an increase in demand for perfusion graduates. The decline in programs and graduates has also been noted in anesthesia and surgical residency programs. The shift is caused by a combination of economic and clinical factors. First, decreased reimbursement has led to reallocation of hospital resources. Second, the original enthusiasm for beating heart coronary artery bypass surgery was grossly overestimated and has led to further reallocation of hospital resources and denigration of cardiopulmonary bypass. This paper describes two models of perfusion education programs: serial perfusion education model (SPEM) and the distributed perfusion education model (DPEM). Arguments are presented that the SPEM has some serious limitations and challenges for long-term economic survival. The authors feel the DPEM along with dependence on tuition funding can survive the current clinical and economic conditions and allow the profession to adapt to changes in scope of practice. PMID:16524152

  10. Lipids and the malarial parasite*

    PubMed Central

    Holz, George G.

    1977-01-01

    Merozoite endocytosis initiates Plasmodium development in a vacuole bounded by an erythrocyte-derived membrane, whose asymmetrical distribution of lipids and proteins is reversed in its orientation with respect to the parasite plasma membrane. Reorientation may accompany the proliferation of the membrane associated with the parasite's growth and phagocytic and pinocytic feeding. Increases in the membrane surface area of the parasite, and in some cases of the erythrocyte, parallel parasite growth and segmentation. Augmentation of all the membrane systems of the infected erythrocyte causes the lipid content to rise rapidly, but the parasite lipid composition differs from that of the erythrocyte in many respects: it is higher in diacyl phosphatidylethanolamine, phosphatidylinositol, polyglycerol phosphatides, diacylglycerols, unesterified fatty acids, triacylglycerols, and hexadecanoic and octadecenoic fatty acids and lower in sphingomyelin, phosphatidylserine, alkoxy phosphatidylethanolamine, cholesterol, and polyunsaturated fatty acids. Active lipid metabolism accompanies the membrane proliferation associated with feeding, growth, and reproduction. Plasmodium is incapable of de novo biosynthesis of fatty acids and cholesterol; however, it can fabricate its glycerides and phosphoglycerides with host-supplied fatty acids, nitrogenous bases, alcohols, ATP, and coenzyme A, and can generate the glyceryl moiety during glycolysis. Cholesterol is obtained from the host but nothing is known of sphingolipid origins. Lipid metabolism of the parasite may be associated with alterations in the amounts of octadecenoic fatty acids and cholesterol in the erythrocyte plasma membrane, which in turn are responsible for changes in permeability and fragility. PMID:412602

  11. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... JavaScript. A pulmonary ventilation/perfusion scan involves two nuclear scan tests to measure breathing (ventilation) and circulation ( ... In: Mettler FA, Guiberteau MJ, eds. Essentials of Nuclear Medicine Imaging . 6th ed. Philadelphia, PA: Elsevier Saunders; ...

  12. The nitric oxide donor S-nitrosoglutathione reduces apoptotic primary liver cell loss in a three-dimensional perfusion bioreactor culture model developed for liver support.

    PubMed

    Prince, Jose M; Vodovotz, Yoram; Baun, Matthew J; Monga, Satdarshan Pal; Billiar, Timothy R; Gerlach, Jörg C

    2010-03-01

    Artificial extracorporeal support for hepatic failure has met with limited clinical success. In hepatocytes, nitric oxide (NO) functions as an antiapoptotic modulator in response to a variety of stresses. We hypothesized that NO administration would yield improved viability and hepatocellular restructuring in a four-compartment, hollow fiber-based bioreactor with integral oxygenation for dynamic three-dimensional perfusion of hepatic cells in bioartificial liver support systems. Isolated adult rat liver cells were placed in culture medium alone (control) or medium supplemented with various concentrations of an NO donor (S-nitrosoglutathione [GSNO]) in the bioreactors. Media samples were obtained from the cell perfusion circuit to monitor cellular response. After 24 and 72 h, histology biopsies were taken to investigate spontaneous restructuring of the cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to quantify apoptotic nuclei. Control bioreactors exhibited 47.9 +/- 2.9% (mean +/- standard error of the mean) apoptotic nuclei. In contrast, NO-treated bioreactors exhibited a biphasic response. Fewer apoptotic nuclei were seen in the 200 and 500 microM GSNO groups (14.4 +/- 0.4%). No effect was observed in the 10 microM GSNO group (47.3%), and increased TUNEL staining was observed in the 1000 microM GSNO group (82.6%). Media lactate dehydrogenase levels were lower in bioreactor groups treated with 200 or 500 microM GSNO (310 +/- 38 IU/L) compared with the control group (919 +/- 188 IU/L; p < 0.05). Protein synthesis was not affected, as measured by albumin levels in the media (115 +/- 19 microg/day/cell inoculum in GSNO-treated bioreactors at 24 h vs. 110 +/- 13 in controls; p = 0.851). Histologically, all of the bioreactor groups exhibited liver cell aggregates with some attached to the bioreactor capillaries. Increased numbers of cells in the aggregates and superior spontaneous restructuring of the cells were seen at

  13. Intracellular Targeting Specificity of Novel Phthalocyanines Assessed in a Host-Parasite Model for Developing Potential Photodynamic Medicine

    PubMed Central

    Dutta, Sujoy; Ongarora, Benson G.; Li, Hairong; Vicente, Maria da Graca H.; Kolli, Bala K.; Chang, Kwang Poo

    2011-01-01

    Photodynamic therapy, unlikely to elicit drug-resistance, deserves attention as a strategy to counter this outstanding problem common to the chemotherapy of all diseases. Previously, we have broadened the applicability of this modality to photodynamic vaccination by exploiting the unusual properties of the trypanosomatid protozoa, Leishmania, i.e., their innate ability of homing to the phagolysosomes of the antigen-presenting cells and their selective photolysis therein, using transgenic mutants endogenously inducible for porphyrin accumulation. Here, we extended the utility of this host-parasite model for in vitro photodynamic therapy and vaccination by exploring exogenously supplied photosensitizers. Seventeen novel phthalocyanines (Pcs) were screened in vitro for their photolytic activity against cultured Leishmania. Pcs rendered cationic and soluble (csPcs) for cellular uptake were phototoxic to both parasite and host cells, i.e., macrophages and dendritic cells. The csPcs that targeted to mitochondria were more photolytic than those restricted to the endocytic compartments. Treatment of infected cells with endocytic csPcs resulted in their accumulation in Leishmania-containing phagolysosomes, indicative of reaching their target for photodynamic therapy, although their parasite versus host specificity is limited to a narrow range of csPc concentrations. In contrast, Leishmania pre-loaded with csPc were selectively photolyzed intracellularly, leaving host cells viable. Pre-illumination of such csPc-loaded Leishmania did not hinder their infectivity, but ensured their intracellular lysis. Ovalbumin (OVA) so delivered by photo-inactivated OVA transfectants to mouse macrophages and dendritic cells were co-presented with MHC Class I molecules by these antigen presenting cells to activate OVA epitope-specific CD8+T cells. The in vitro evidence presented here demonstrates for the first time not only the potential of endocytic csPcs for effective photodynamic therapy

  14. [Anisakiasis - a little-known parasitic zoonosis].

    PubMed

    Bardoň, Jan; Harna, Jiří; Pijáček, Martin

    2013-06-01

    Parasites of the family Anisakidae cause enteric parasitic zoonoses developing after consumption of inadequately cooked marine fish. Cases of such diseases are reported mainly from Japan or other countries where raw or uncooked fish are traditionally consumed. The presented short communication briefly reports detection of larvae of Pseudoterranova spp., parasites of the family Anisakidae, in a fresh chilled angler-fish (Lophius piscatorius) bought at a retail store in the Czech Republic.

  15. A pump-free membrane-controlled perfusion microfluidic platform

    PubMed Central

    Goral, Vasiliy N.; Tran, Elizabeth; Yuen, Po Ki

    2015-01-01

    In this article, we present a microfluidic platform for passive fluid pumping for pump-free perfusion cell culture, cell-based assay, and chemical applications. By adapting the passive membrane-controlled pumping principle from the previously developed perfusion microplate, which utilizes a combination of hydrostatic pressure generated by different liquid levels in the wells and fluid wicking through narrow strips of a porous membrane connecting the wells to generate fluid flow, a series of pump-free membrane-controlled perfusion microfluidic devices was developed and their use for pump-free perfusion cell culture and cell-based assays was demonstrated. Each pump-free membrane-controlled perfusion microfluidic device comprises at least three basic components: an open well for generating fluid flow, a micron-sized deep chamber/channel for cell culture or for fluid connection, and a wettable porous membrane for controlling the fluid flow. Each component is fluidically connected either by the porous membrane or by the micron-sized deep chamber/channel. By adapting and incorporating the passive membrane-controlled pumping principle into microfluidic devices, all the benefits of microfluidic technologies, such as small sample volumes, fast and efficient fluid exchanges, and fluid properties at the micro-scale, can be fully taken advantage of with this pump-free membrane-controlled perfusion microfluidic platform. PMID:26392835

  16. A new model for myxosporean (Myxozoa) development explains the endogenous budding phenomenon, the nature of cell within cell life stages and evolution of parasitism from a cnidarian ancestor.

    PubMed

    Morris, D J

    2012-08-01

    The phylum Myxozoa is composed of endoparasitic species that have predominately been recorded within aquatic vertebrates. The simple body form of a trophic cell containing other cells within it, as observed within these hosts, has provided few clues to relationships with other organisms. In addition, the placement of the group using molecular phylogenies has proved very difficult, although the majority of analyses now suggest that they are cnidarians. There have been relatively few studies of myxozoan stages within invertebrate hosts, even though these exhibit multicellular and sexual stages that may provide clues to myxozoan evolution. Therefore an ultrastructural examination of a myxozoan infection of a freshwater oligochaete was conducted, to reassess and formulate a model for myxozoan development in these hosts. This deemed that meiosis occurs within the oligochaete, but that fertilisation is not immediate. Rather, the resultant haploid germ cell (oocyte) is engulfed by a diploid sporogonic cell (nurse cell) to form a sporoplasm. It is this sporoplasm that infects the fish, resulting in the multicellular stages observed. Fertilisation occurs after the parasites leave the fish and enter the oligochaete host. The nurse cell/oocyte model explains previously conflicting evidence in the literature regarding myxosporean biology, and aligns phenomena considered distinctive to the Myxozoa, such as endogenous budding and cell within cell development, with processes recorded in cnidarians. Finally, the evolutionary origin of the Myxozoa as cnidarian parasites of ova is hypothesised.

  17. Nifedipine increases fetoplacental perfusion.

    PubMed

    Karahanoglu, Ertugrul; Altinboga, Orhan; Akpinar, Funda; Demirdag, Erhan; Ozdemirci, Safak; Akyol, Aysegul; Yalvac, Serdar

    2017-01-01

    Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6±2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the "continuity equation", to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166±73.81 beat.cm3/min to 220±83.3 beat.cm3/min. Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP.

  18. Heart failure diagnostics based on ventilation/perfusion single photon emission computed tomography pattern and quantitative perfusion gradients.

    PubMed

    Jögi, Jonas; Palmer, John; Jonson, Björn; Bajc, Marika

    2008-08-01

    Left heart failure (LHF) is a common and frequently overlooked condition owing to insufficient diagnostic methods. This can potentially delay onset of treatment. Our clinical experience with ventilation/perfusion single photon emission computed tomography (V/P SPECT) indicates that perfusion shows an antigravitational distribution pattern in LHF. The aim of the study was to test the hypothesis that LHF diagnosis can be made on the basis of V/P SPECT, and to develop and perform a first evaluation of objective parameters for LHF diagnostics in terms of perfusion gradients. This retrospective study included 247 consecutive patients with clinical suspicion of pulmonary embolism (PE), who were examined with V/P SPECT. Perfusion gradients were developed and quantified in dorso-ventral and cranio-caudal directions. Quantitative results were compared with visual interpretation of patients with normal and heart failure patterns. Patients with LHF pattern were retrospectively followed up by review of medical records to confirm or discard heart failure diagnosis at the time of V/P SPECT examination. LHF pattern on V/P SPECT was identified in 36 patients (15%), normal ventilation/perfusion pattern was found in 67 patients (27%), and PE in 62 patients (25%). The follow-up confirmed heart failure diagnosis in 32 of the 36 cases with LHF pattern, leading to a positive predictive value of 88% for LHF diagnosis based on V/P SPECT. Dorso-ventral perfusion gradients discriminated normal from LHF patients. In patients with suspected PE, LHF is common. Appropriate V/P SPECT pattern recognition, supported by objectively determined dorso-ventral perfusion gradients, allows the diagnosis of LHF. A positive perfusion gradient in the dorso-ventral direction should lead to consideration of heart failure as a possible explanation for the symptoms in these patients.

  19. A syndromic approach to common parasitic diseases

    PubMed Central

    Shafran, Stephen D.; Chow, Anthony W.

    1985-01-01

    Standard textbooks discuss parasitic disease according to specific organisms. In contrast, patients with parasitic infections present to physicians with a variety of clinical manifestations that may involve any of several organ systems and that often mimic nonparasitic diseases. A syndromic approach to the clinical situation may help the physician in considering the most important parasitic agents. Many parasitic infections can be acquired in temperate climates. While often considered tropical or exotic, other parasitic diseases are now seen more frequently in developed countries because of immigration and increased world travel. In this review the clinical syndromes associated with common parasitic diseases in North America are discussed, with an emphasis on risk factors and diagnosis of specific infections. PMID:4042057

  20. Intestinal parasitic infection.

    PubMed

    Park, Mi-Suk; Kim, Ki Whang; Ha, Hyun Kwon; Lee, Dong Ho

    2008-01-01

    In general, gastrointestinal tract is the primary involvement site of parasites during their life cycle. In this article, we will describe amebiasis, ascariasis, and anisakiasis among the many common intestinal parasitic diseases. We will review the epidemiology, life cycles, clinical manifestations and complications, and illustrate detailed imaging findings of intestinal parasites. Recognizing features of parasitic infection is important to establish an early diagnosis that leads to prompt treatment and helps avoid unnecessary surgery.

  1. Fractal analysis in radiological and nuclear medicine perfusion imaging: a systematic review.

    PubMed

    Michallek, Florian; Dewey, Marc

    2014-01-01

    To provide an overview of recent research in fractal analysis of tissue perfusion imaging, using standard radiological and nuclear medicine imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and to discuss implications for different fields of application. A systematic review of fractal analysis for tissue perfusion imaging was performed by searching the databases MEDLINE (via PubMed), EMBASE (via Ovid) and ISI Web of Science. Thirty-seven eligible studies were identified. Fractal analysis was performed on perfusion imaging of tumours, lung, myocardium, kidney, skeletal muscle and cerebral diseases. Clinically, different aspects of tumour perfusion and cerebral diseases were successfully evaluated including detection and classification. In physiological settings, it was shown that perfusion under different conditions and in various organs can be properly described using fractal analysis. Fractal analysis is a suitable method for quantifying heterogeneity from radiological and nuclear medicine perfusion images under a variety of conditions and in different organs. Further research is required to exploit physiologically proven fractal behaviour in the clinical setting. • Fractal analysis of perfusion images can be successfully performed. • Tumour, pulmonary, myocardial, renal, skeletal muscle and cerebral perfusion have already been examined. • Clinical applications of fractal analysis include tumour and brain perfusion assessment. • Fractal analysis is a suitable method for quantifying perfusion heterogeneity. • Fractal analysis requires further research concerning the development of clinical applications.

  2. The isolated perfused human skin flap model: A missing link in skin penetration studies?

    PubMed

    Ternullo, Selenia; de Weerd, Louis; Flaten, Gøril Eide; Holsæter, Ann Mari; Škalko-Basnet, Nataša

    2017-01-01

    Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Quantitative Analysis of Peripheral Tissue Perfusion Using Spatiotemporal Molecular Dynamics

    PubMed Central

    Lee, Jungsul; Koh, Gou Young; Kwon, Kihwan; Choi, Chulhee

    2009-01-01

    Background Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging. Methodology/Principal Findings We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1. Conclusions/Significance We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis. PMID:19169354

  4. Mucosal blood flow measurements using laser Doppler perfusion monitoring

    PubMed Central

    Hoff, Dag Arne Lihaug; Gregersen, Hans; Hatlebakk, Jan Gunnar

    2009-01-01

    Perfusion of individual tissues is a basic physiological process that is necessary to sustain oxygenation and nutrition at a cellular level. Ischemia, or the insufficiency of perfusion, is a common mechanism for tissue death or degeneration, and at a lower threshold, a mechanism for the generation of sensory signalling including pain. It is of considerable interest to study perfusion of peripheral abdominal tissues in a variety of circumstances. Microvascular disease of the abdominal organs has been implicated in the pathogenesis of a variety of disorders, including peptic ulcer disease, inflammatory bowel disease and chest pain. The basic principle of laser Doppler perfusion monitoring (LDPM) is to analyze changes in the spectrum of light reflected from tissues as a response to a beam of monochromatic laser light emitted. It reflects the total local microcirculatory blood perfusion, including perfusion in capillaries, arterioles, venules and shunts. During the last 20-25 years, numerous studies have been performed in different parts of the gastrointestinal (GI) tract using LDPM. In recent years we have developed a multi-modal catheter device which includes a laser Doppler probe, with the intent primarily to investigate patients suffering from functional chest pain of presumed oesophageal origin. Preliminary studies show the feasibility of incorporating LDPM into such catheters for performing physiological studies in the GI tract. LDPM has emerged as a research and clinical tool in preference to other methods; but, it is important to be aware of its limitations and account for them when reporting results. PMID:19132770

  5. CT perfusion: principles, applications, and problems

    NASA Astrophysics Data System (ADS)

    Lee, Ting-Yim

    2004-10-01

    The fast scanning speed of current slip-ring CT scanners has enabled the development of perfusion imaging techniques with intravenous injection of contrast medium. In a typical CT perfusion study, contrast medium is injected and rapid scanning at a frequency of 1-2 Hz is used to monitor the first circulation of the injected contrast medium through a 1-2 cm thick slab of tissue. From the acquired time-series of CT images, arteries can be identified within the tissue slab to derive the arterial contrast concentration curve, Ca(t) while each individual voxel produces a tissue residue curve, Q(t) for the corresponding tissue region. Deconvolution between the measured Ca(t) and Q(t) leads to the determination of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in brain studies. In this presentation, an important application of CT perfusion in acute stroke studies - the identification of the ischemic penumbra via the CBF/CBV mismatch and factors affecting the quantitative accuracy of deconvolution, including partial volume averaging, arterial delay and dispersion are discussed.

  6. Parasites, Plants, and People.

    PubMed

    Johnson, Marion; Moore, Tony

    2016-06-01

    Anthelminthic resistance is acknowledged worldwide and is a major problem in Aotearoa New Zealand, thus alternative parasite management strategies are imperative. One Health is an initiative linking animal, human, and environmental health. Parasites, plants, and people illustrate the possibilities of providing diverse diets for stock thereby lowering parasite burdens, improving the cultural wellbeing of a local community, and protecting the environment.

  7. Cathepsin B- and L-like cysteine protease activities during the in vitro development of Hysterothylacium aduncum (Nematoda: Anisakidae), a worldwide fish parasite.

    PubMed

    Malagón, David; Díaz-López, Manuel; Benítez, Rocío; Adroher, Francisco Javier

    2010-03-01

    Proteinases play an important role as virulence factors both in the life-cycle of parasites and in the pathogen-host relationship. Hysterothylacium aduncum is a worldwide fish parasite nematode which has been associated with non-invasive anisakidosis and allergic responses to fish consumption in humans. Cysteine proteinases have been associated with allergy to plant pollens, detergents and dust mites. In this study the presence of two types of cysteine proteinases (cathepsin B and cathepsin L) during in vitro development of H. aduncum is investigated. Specific fluorescent substrates were used to determine cathepsin activities. The activity detected with substrate Z-FR-AMC was identified as cathepsin L (optimum pH=5.5; range 3.5-6.5). Cathepsin B activity was only identified with Z-RR-AMC (optimum pH=7.0-7.5; range 5.0-8.0). The start of cultivation led to increased activity of both cathepsins (1.8-fold for cathepsin B and 6.3-fold for cathepsin L). These activities varied according to the developmental stage. Cathepsin B activity decreased after M4, returning to its initial level. Cathepsin L activity also decreased after M4, but still maintained a high level (4-6 times the initial level) in adult stages. Having considered these activity variations and the optimum pH values, we suggest that cathepsin L has a role in digestive processes while cathepsin B could be involved in cuticle renewal, among other possible functions.

  8. Genetic analysis and development of species-specific PCR assays based on ITS-1 region of rRNA in bovine Eimeria parasites.

    PubMed

    Kawahara, Fumiya; Zhang, Guohong; Mingala, Claro N; Tamura, Yu; Koiwa, Masateru; Onuma, Misao; Nunoya, Tetsuo

    2010-11-24

    At present, morphological characteristics of oocyst is the only achievable method for the identification of bovine coccidia to the species level. In this study, the internal transcribed spacer 1 (ITS-1) region of ribosomal RNA genes of six bovine Eimeria species; E. alabamensis, E. auburnensis, E. bovis, E. cylindrica, E. ellipsoidalis and E. zuernii, were sequenced and analyzed the phylogenetic relationship among them. In pair-wise alignment, the sequences among the same species had high homology of over 90%. E. bovis and E. zuernii were closely related within the same cluster. This cluster and E. alabamensis were distant from major cluster of bovine coccidia that included E. auburnensis, E. cylindrica and E. ellipsoidalis. Species-specific PCR assays based on the amplification of the ITS-1 region were also developed to identify the 6 pathogens. The ITS-1 region of each Eimeria species had sufficient inter-specific sequence variation enough to design the primer sets that differentially amplified each target species. This PCR assay for the detection and differentiation of Eimeria parasite showed higher sensitivity when compared to the conventional oocyst-morphological examination. This is the first attempt for the identification of 6 bovine Eimeria parasites in the genomic level and may provide as useful methods for diagnosis and epidemiology of bovine coccidial infection.

  9. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite.

    PubMed

    Borges-Pereira, Lucas; Meissner, Kamila Anna; Wrenger, Carsten; Garcia, Célia R S

    2017-03-11

    Plasmodium falciparum is the causative agent of the most dangerous form of malaria in humans. It has been reported that the P. falciparum genome encodes for a single ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), an enzyme that hydrolyzes extracellular tri- and di-phosphate nucleotides. The E-NTPDases are known for participating in invasion and as a virulence factor in many pathogenic protozoa. Despite its presence in the parasite genome, currently, no information exists about the activity of this predicted protein. Here, we show for the first time that P. falciparum E-NTPDase is relevant for parasite lifecycle as inhibition of this enzyme impairs the development of P. falciparum within red blood cells (RBCs). ATPase activity could be detected in rings, trophozoites, and schizonts, as well as qRT-PCR, confirming that E-NTPDase is expressed throughout the intraerythrocytic cycle. In addition, transfection of a construct which expresses approximately the first 500 bp of an E-NTPDase-GFP chimera shows that E-NTPDase co-localizes with the endoplasmic reticulum (ER) in the early stages and with the digestive vacuole (DV) in the late stages of P. falciparum intraerythrocytic cycle.

  10. Transcript maturation in apicomplexan parasites

    PubMed Central

    Suvorova, Elena S.; White, Michael W.

    2014-01-01

    Summary The complex life cycles of apicomplexan parasites are associated with dynamic changes of protein repertoire. In Toxoplasma gondii, global analysis of gene expression demonstrates that dynamic changes in mRNA levels unfold in a serial cascade during asexual replication and up to 50% of encoded genes are unequally expressed in development. Recent studies indicate transcription as well as mRNA processing have important roles in fulfilling the “just-in-time” delivery of proteins to parasite growth and development. The prominence of post-transcriptional mechanisms in the Apicomplexa was demonstrated by mechanistic studies of the critical RNA-binding proteins and regulatory kinases. However, it is still early in our understanding of how transcription and post-transcriptional mechanisms are balanced to produce adequate numbers of specialized forms that is required to complete the parasite life cycle. PMID:24934558

  11. A compact instrument to measure perfusion of vasculature in transplanted maxillofacial free flaps

    NASA Astrophysics Data System (ADS)

    Kolodziejski, Noah J.; Stapels, Christopher J.; McAdams, Daniel R.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Ward, Brent B.; Vartarian, Mark; Feinberg, Stephen E.; Lee, Seung Yup; Parikh, Urmi; Mycek, Mary-Ann; Christian, James F.

    2016-03-01

    The vascularization and resulting perfusion of transferred tissues are critical to the success of grafts in buried free flap transplantations. To enable long-term clinical monitoring of grafted tissue perfusion during neovascularization and endothelialization, we are developing an implantable instrument for the continuous monitoring of perfusion using diffuse correlation spectroscopy (DCS), and augmented with diffuse reflectance spectroscopy (DRS). This work discusses instrument construction, integration, and preliminary results using a porcine graft model.

  12. Early intrauterine embryonic development of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost Merluccius merluccius (L., 1758) (Gadiformes: Merlucciidae).

    PubMed

    Swiderski, Zdzisław; Miquel, Jordi; Torres, Jordi; Delgado, Eulàlia

    2013-07-01

    The early intrauterine embryonic development of the bothriocephalidean cestode Clestobothrium crassiceps (Rudolphi, 1819), a parasite of the teleost Merluccius merluccius (L., 1758), was studied by means of light (LM) and transmission electron microscopy (TEM). Contrary to the generic diagnosis given in the CABI Keys to the cestode parasites of vertebrates, the eggs of C. crassiceps, the type of species of Clestobothrium Lühe, 1899, are operculate and embryonated. Our LM and TEM results provide direct evidence that an operculum is present and that the eggs exhibit various stages of intrauterine embryonic development, and in fact represent a good example of early ovoviviparity. The intrauterine eggs of this species are polylecithal and contain numerous vitellocytes, generally ∼30, which are pushed to the periphery and remain close to the eggshell, whereas the dividing zygote and later the early embryo remain in the egg centre. During early intrauterine embryonic development, several cleavage divisions take place, which result in the formation of three types of blastomeres, i.e. macro-, meso- and micromeres. These can be readily differentiated at the TEM level, not only by their size, but also by the ultrastructural characteristics of their nuclei and cytoplasmic organelles. The total number of blastomeres in these early embryos, enclosed within the electron-dense eggshells, can be up to ∼20 cells of various sizes and characteristics. Mitotic divisions of early blastomeres were frequently observed at both LM and TEM levels. Simultaneously with the mitotic cleavage divisions leading to blastomere multiplication and their rapid differentiation, there is also a deterioration of some blastomeres, mainly micromeres. A similar degeneration of vitellocytes begins even earlier. Both processes show a progressive degeneration of both vitellocytes and micromeres, and are good examples of apoptosis, a process that provides nutritive substances, including lipids, for the

  13. The Nitric Oxide Donor S-Nitrosoglutathione Reduces Apoptotic Primary Liver Cell Loss in a Three-Dimensional Perfusion Bioreactor Culture Model Developed for Liver Support

    PubMed Central

    Prince, Jose M.; Vodovotz, Yoram; Baun, Matthew J.; Monga, Satdarshan Pal; Billiar, Timothy R.

    2010-01-01

    Introduction Artificial extracorporeal support for hepatic failure has met with limited clinical success. In hepatocytes, nitric oxide (NO) functions as an antiapoptotic modulator in response to a variety of stresses. We hypothesized that NO administration would yield improved viability and hepatocellular restructuring in a four-compartment, hollow fiber-based bioreactor with integral oxygenation for dynamic three-dimensional perfusion of hepatic cells in bioartificial liver support systems. Methods Isolated adult rat liver cells were placed in culture medium alone (control) or medium supplemented with various concentrations of an NO donor (S-nitrosoglutathione [GSNO]) in the bioreactors. Media samples were obtained from the cell perfusion circuit to monitor cellular response. After 24 and 72 h, histology biopsies were taken to investigate spontaneous restructuring of the cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to quantify apoptotic nuclei. Results Control bioreactors exhibited 47.9 ± 2.9% (mean ± standard error of the mean) apoptotic nuclei. In contrast, NO-treated bioreactors exhibited a biphasic response. Fewer apoptotic nuclei were seen in the 200 and 500 μM GSNO groups (14.4 ± 0.4%). No effect was observed in the 10 μM GSNO group (47.3%), and increased TUNEL staining was observed in the 1000 μM GSNO group (82.6%). Media lactate dehydrogenase levels were lower in bioreactor groups treated with 200 or 500 μM GSNO (310 ± 38 IU/L) compared with the control group (919 ± 188 IU/L; p < 0.05). Protein synthesis was not affected, as measured by albumin levels in the media (115 ± 19 μg/day/cell inoculum in GSNO-treated bioreactors at 24 h vs. 110 ± 13 in controls; p = 0.851). Histologically, all of the bioreactor groups exhibited liver cell aggregates with some attached to the bioreactor capillaries. Increased numbers of cells in the aggregates and

  14. An interplay between 2 signaling pathways: Melatonin-cAMP and IP{sub 3}–Ca{sup 2+} signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum

    SciTech Connect

    Furuyama, Wakako; Enomoto, Masahiro; Mossaad, Ehab; Kawai, Satoru; Mikoshiba, Katsuhiko; Kawazu, Shin-ichiro

    2014-03-28

    Highlights: • A melatonin receptor antagonist blocked Ca{sup 2+} oscillation in P. falciparum and inhibited parasite growth. • P. falciparum development is controlled by Ca{sup 2+}- and cAMP-signaling pathways. • The cAMP-signaling pathway at ring form and late trophozoite stages governs parasite growth of P. falciparum. - Abstract: Plasmodium falciparum spends most of its asexual life cycle within human erythrocytes, where proliferation and maturation occur. Development into the mature forms of P. falciparum causes severe symptoms due to its distinctive sequestration capability. However, the physiological roles and the molecular mechanisms of signaling pathways that govern development are poorly understood. Our previous study showed that P. falciparum exhibits stage-specific spontaneous Calcium (Ca{sup 2+}) oscillations in ring and early trophozoites, and the latter was essential for parasite development. In this study, we show that luzindole (LZ), a selective melatonin receptor antagonist, inhibits parasite growth. Analyses of development and morphology of LZ-treated P. falciparum revealed that LZ severely disrupted intraerythrocytic maturation, resulting in parasite death. When LZ was added at ring stage, the parasite could not undergo further development, whereas LZ added at the trophozoite stage inhibited development from early into late schizonts. Live-cell Ca{sup 2+} imaging showed that LZ treatment completely abolished Ca{sup 2+} oscillation in the ring forms while having little effect on early trophozoites. Further, the melatonin-induced cAMP increase observed at ring and late trophozoite stage was attenuated by LZ treatment. These suggest that a complex interplay between IP{sub 3}–Ca{sup 2+} and cAMP signaling pathways is involved in intraerythrocytic development of P. falciparum.

  15. Evaluation of the role of galectins in parasite immunity.

    PubMed

    Preston, Sarah; Dunphy, Jillian; Beddoe, Travis; Meeusen, Els; Young, Anna

    2015-01-01

    Galectin-11 and galectin-14 are ruminant galectins involved in parasitic infections. Although their roles in parasite immunity are still being elucidated, its appears that their functions are parasite specific. In gastrointestinal infections with the nematode Haemonchus contortus, both galectin-11 and galectin-14 appear to be protective. However, in a chronic infection of liver fluke, Fasciola hepatica, these galectins may aid parasite survival. This chapter discusses the methods designed to study parasitic infections in sheep, which have provided us with insight into the functions of galectin-11 and galectin-14 during host-parasite interactions. These methods include parasite cultivation and infection, galectin staining of host and parasite tissue, surface staining of parasites with recombinant galectins and in vitro assays to monitor the effect of galectins on larval development.

  16. Encystation of entamoeba parasites.

    PubMed

    Eichinger, D

    1997-07-01

    Entamoeba histolytica is a protozoan parasite of humans, and the causitive agent of intestinal amebiasis. The disease-causing stage of the parasite is an osmotically sensitive ameboid form, which differentiates into a thick-walled cyst for transmission from person to person. The conditions within the human intestine that induce encystment of the amoeba are unknown, but studies using an amoebic parasite of reptiles are now yielding information about the molecules and host:parasite interactions involved in the process. An understanding of the amoeba's obligatory encystment pathway should provide an approach for interrupting the transmission of this parasite, for which there is currently no vaccine.

  17. Nutrition and parasite interaction.

    PubMed

    Coop, R L; Holmes, P H

    1996-01-01

    This overview focuses on the interaction between nutritional status and gastrointestinal nematode infection in ruminants and considers: (i) the influence of the parasite on host metabolism; and (ii) the effect of host nutrition on the establishment and survival of parasite populations, the development of the host-immune response and the pathophysiology of infection. Gastrointestinal nematodes reduce voluntary feed intake and efficiency of feed utilisation, a key feature being an increased endogenous loss of protein into the gastrointestinal tract. Overall there is movement of protein from productive processes into repair of the gastrointestinal tract, synthesis of plasma proteins and mucoprotein production. Although reduction in feed intake is a major factor contributing to the reduced performance of parasitised ruminants, the underlying mechanisms of the anorexia are poorly understood. Supplementation of the diet with additional protein does not appear to affect initial establishment of nematode infections but the pathophysiological consequences are generally more severe on lower planes of protein nutrition. The main effect of protein supplementation is to increase the rate of acquisition of immunity and increase resistance to reinfection and this has been associated with an enhanced cellular immune response in the gastrointestinal mucosa. The unresponsiveness of the young lamb can be improved by dietary protein supplementation. Recent trials have shown that growing sheep offered a free choice between a low and a high protein ration are able to modify their diet selection in order to alleviate the increase in protein requirements which result from gastrointestinal nematode infection. Studies on the influence of nutrition on the expression of genotype have shown that the benefits of a superior genotype are not lost on a low protein diet whereas a high protein diet can partially emeliorate the disadvantages of an inferior genotype. In addition to dietary protein

  18. Combined supine and prone quantitative myocardial perfusion SPECT: method development and clinical validation in patients with no known coronary artery disease.

    PubMed

    Nishina, Hidetaka; Slomka, Piotr J; Abidov, Aiden; Yoda, Shunichi; Akincioglu, Cigdem; Kang, Xingping; Cohen, Ishac; Hayes, Sean W; Friedman, John D; Germano, Guido; Berman, Daniel S

    2006-01-01

    Acquisition in the prone position has been demonstrated to improve the specificity of visually analyzed myocardial perfusion SPECT (MPS) for detecting coronary artery disease (CAD). However, the diagnostic value of prone imaging alone or combined acquisition has not been previously described using quantitative analysis. A total of 649 patients referred for MPS comprised the study population. Separate supine and prone normal limits were derived from 40 males and 40 females with a low likelihood (LLk) of CAD using a 3 average-deviation cutoff for all pixels on the polar map. These limits were applied to the test population of 369 consecutive patients (65% males; age, 65 +/- 13 y; 49% exercise stress) without known CAD who had diagnostic coronary angiography within 3 mo of MPS. Total perfusion deficit (TPD), defined as a product of defect extent and severity scores, was obtained for supine (S-TPD), prone (P-TPD), and combined supine-prone datasets (C-TPD). The angiographic group was randomly divided into 2 groups for deriving and validating optimal diagnostic cutoffs. Normalcy rates were validated in 2 additional groups of consecutive LLk patients: unselected patients (n = 100) and patients with body mass index >30 (n = 100). C-TPD had a larger area under the receiver-operating-characteristic (ROC) curve than S-TPD or P-TPD for identification of stenosis >or=70% (0.86, 0.88, and 0.90 for S-TPD, P-TPD, and C-TPD, respectively; P < 0.05). In the validation group, sensitivity for P-TPD was lower than for S- or C-TPD (P < 0.05). C-TPD yielded higher specificity than S-TPD and a trend toward higher specificity than P-TPD (65%, 83%, and 86% for S-, P-, and C-TPD, respectively, P < 0.001; vs. S-TPD and P = 0.06 vs. P-TPD). Normalcy rates for C-TPD were higher than for S-TPD in obese LLk patients (78% vs. 95%, P < 0.001). Combined supine-prone quantification significantly improves the area under the ROC curve and specificity of MPS in the identification of obstructive CAD

  19. The stripe sign: correlation of radionuclide ventilation and perfusion with He-3 magnetic resonance lung imaging

    PubMed

    Teates; Brookeman; Daniel; Truwit; Parekh; Mugler; de Lange EE

    1999-10-01

    PURPOSE: The aim of this study was to correlate regional ventilation and perfusion images and perfusion SPECT with images made using a newly developed magnetic resonance ventilation (MRV) method. MATERIALS AND METHODS: The investigation included a single patient with chronic obstructive pulmonary disease and a healthy control participant. Ventilation and perfusion images using Xe-133 and Tc-99m MAA, including perfusion SPECT, were compared with single-breath MRV with hyperpolarized He-3. RESULTS: Ventilation and perfusion defects correspond to areas of poor ventilation on MRV. High-resolution MRV images show preservation of bronchi and acinus units in areas of the "stripe sign" on the V/Q study. CONCLUSIONS: MRV imaging confirms that the stripe sign seen on nuclear perfusion imaging correlates with subsegmental preserved lung. MRV imaging has the potential for high-resolution innovative studies of subsegmental lung function, using either He-3 or Xe-129 hyperpolarized gases.

  20. Parasites and supernormal manipulation.

    PubMed Central

    Holen, Ø. H.; Saetre, G. P.; Slagsvold, T.; Stenseth, N. C.

    2001-01-01

    Social parasites may exploit their hosts by mimicking other organisms that the hosts normally benefit from investing in or responding to in some other way. Some parasites exaggerate key characters of the organisms they mimic, possibly in order to increase the response from the hosts. The huge gape and extreme begging intensity of the parasitic common cuckoo chick (Cuculus canorus) may be an example. In this paper, the evolutionary stability of manipulating hosts through exaggerated signals is analysed using game theory. Our model indicates that a parasite's signal intensity must be below a certain threshold in order to ensure acceptance and that this threshold depends directly on the rate of parasitism. The only evolutionarily stable strategy (ESS) combination is when hosts accept all signallers and parasites signal at their optimal signal intensity, which must be below the threshold. Supernormal manipulation by parasites is only evolutionarily stable under sufficiently low rates of parasitism. If the conditions for the ESS combination are not satisfied, rejector hosts can invade using signal intensity as a cue for identifying parasites. These qualitative predictions are discussed with respect to empirical evidence from parasitic mimicry systems that have been suggested to involve supernormal signalling, including evicting avian brood parasites and insect-mimicking Ophrys orchids. PMID:11749709

  1. Estimating parasite host range.

    PubMed

    Dallas, Tad; Huang, Shan; Nunn, Charles; Park, Andrew W; Drake, John M

    2017-08-30

    Estimating the number of host species that a parasite can infect (i.e. host range) provides key insights into the evolution of host specialism and is a central concept in disease ecology. Host range is rarely estimated in real systems, however, because variation in species relative abundance and the detection of rare species makes it challenging to confidently estimate host range. We applied a non-parametric richness indicator to estimate host range in simulated and empirical data, allowing us to assess the influence of sampling heterogeneity and data completeness. After validating our method on simulated data, we estimated parasite host range for a sparsely sampled global parasite occurrence database (Global Mammal Parasite Database) and a repeatedly sampled set of parasites of small mammals from New Mexico (Sevilleta Long Term Ecological Research Program). Estimation accuracy varied strongly with parasite taxonomy, number of parasite occurrence records, and the shape of host species-abundance distribution (i.e. the dominance and rareness of species in the host community). Our findings suggest that between 20% and 40% of parasite host ranges are currently unknown, highlighting a major gap in our understanding of parasite specificity, host-parasite network structure, and parasite burdens. © 2017 The Author(s).

  2. The Haustorium, a Specialized Invasive Organ in Parasitic Plants.

    PubMed

    Yoshida, Satoko; Cui, Songkui; Ichihashi, Yasunori; Shirasu, Ken

    2016-04-29

    Parasitic plants thrive by infecting other plants. Flowering plants evolved parasitism independently at least 12 times, in all cases developing a unique multicellular organ called the haustorium that forms upon detection of haustorium-inducing factors derived from the host plant. This organ penetrates into the host stem or root and connects to its vasculature, allowing exchange of materials such as water, nutrients, proteins, nucleotides, pathogens, and retrotransposons between the host and the parasite. In this review, we focus on the formation and function of the haustorium in parasitic plants, with a specific emphasis on recent advances in molecular studies of root parasites in the Orobanchaceae and stem parasites in the Convolvulaceae.

  3. The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

    PubMed Central

    Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

    2014-01-01

    Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

  4. Paradigms for parasite conservation.

    PubMed

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  5. Development of a perfusion ion-exchange chromatography method for the separation of soybean proteins and its application to cultivar characterization.

    PubMed

    Heras, J M; Marina, M L; García, M C

    2007-06-15

    A perfusion ion-exchange chromatography method has been designed, for the first time, for the separation of soybean proteins and its application to the characterization of soybean cultivars. For that purpose, the gradient, the mobile phase composition (buffer concentration, buffer pH, and elution salt), and the temperature were optimized. The method consisted of a two-step gradient (0% B for 2 min and from 0 to 50% B in 10 min) being mobile phase A a 2 0mM borate buffer (pH 9) and mobile phase B a 20 mM borate buffer (pH 9) containing 1M sodium chloride. The procedure used for the preparation of sample solutions was significantly simpler than that proposed by other authors and basically consisted of dissolving in water. This method enabled the separation of soybean proteins from a soybean protein isolate in 11 peaks in about 9 min. The method was used to separate soybean proteins in different commercial soybeans. In general, the 11 peaks yielded by the soybean protein isolate were also observed in the chromatograms of all soybeans. However, the area percentages of every peak in every soybean enabled the differentiation between soybeans. Moreover, the method was also used to separate soybean proteins in the proteic fractions obtained from every soybean. Multivariate methods were used for patterns recognition and the classification of samples.

  6. Development of pulmonary blood flow evaluation method with a dynamic flat-panel detector: quantitative correlation analysis with findings on perfusion scan.

    PubMed

    Tanaka, Rie; Sanada, Shigeru; Fujimura, Masaki; Yasui, Masahide; Hayashi, Norio; Tsuji, Shiro; Okamoto, Hiroyuki; Nanbu, Yuko; Matsui, Osamu

    2010-01-01

    Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X-ray translucency, i.e., pixel values. Thus, decreased blood flow should be observed as a reduction of the variation of X-ray translucency. We performed the present study to investigate the feasibility of pulmonary blood flow evaluation with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14 subjects were obtained with a dynamic FPD system. The changes in pixel value in each local area were measured and mapped on the original image by use of a gray scale in which small and large changes were shown in white and black, respectively. The resulting images were compared to the findings in perfusion scans. The cross-correlation coefficients of the changes in pixel value and radioactivity counts in each local area were also computed. In all patients, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on the mapping image, and a correlation was observed between the distribution of changes in pixel value and those in radioactivity counts (0.7

  7. Quantification of liver perfusion using multidelay pseudocontinuous arterial spin labeling.

    PubMed

    Pan, Xinlei; Qian, Tianyi; Fernandez-Seara, Maria A; Smith, Robert X; Li, Kuncheng; Ying, Kui; Sung, Kyunghyun; Wang, Danny J J

    2016-05-01

    To develop a free-breathing multidelay pseudocontinuous arterial spin labeling (pCASL) technique for quantitative measurement of liver perfusion of the hepatic artery and portal vein, respectively. A navigator-gated pCASL sequence with balanced steady-state free precession (bSSFP) readout was developed and applied on five healthy young volunteers at 3T. Two labeling schemes were performed with the labeling plane applied on the descending aorta above the liver, and perpendicular to the portal vein before its entry to liver to label the hepatic artery and portal vein, respectively. For each labeling scheme, pCASL scans were performed at five or six postlabeling delays between 200 and 2000 msec or 2500 msec with an interval of 400 or 500 msec. Multidelay pCASL images were processed offline with nonrigid motion correction, outlier removal, and fitted for estimation of liver perfusion and transit time. Estimated liver perfusion of the hepatic artery and hepatic portal vein were 21.8 ± 1.9 and 95.1 ± 8.9 mL/100g/min, with the corresponding transit time of 1227.3 ± 355.5 and 667.2 ± 85.0 msec, respectively. The estimated liver perfusion and transit time without motion correction were less reliable with greater residual variance compared to those processed with motion correction (P < 0.05). The liver perfusion measurement using multidelay pCASL showed good correspondence with values noted in the literature. The capability to noninvasively and selectively label the hepatic artery and portal vein is a unique strength of pCASL as compared to other liver perfusion imaging techniques, such as computed tomography perfusion and dynamic contrast-enhanced MRI. © 2015 Wiley Periodicals, Inc.

  8. [Development of a PCR for the detection and quantification of parasitism by Demodex folliculorum infestation in biopsies of skin neoplasms periocular area].

    PubMed

    Tenorio-Abreu, A; Sánchez-España, J C; Naranjo-González, L E; González-Gallego, M C; Hidalgo-Grass, C; Ruíz-Frutos, C

    2016-08-01

    To standardize the relative quantification by mass of tissue parasitism by Demodex folliculorum infestation from neoplastic skin biopsies periocular using molecular amplification to study the possible relationship of the appearance of eyelid basal cell carcinoma with the presence and density of the mite in later works. A quantitative PCR was developed real-time probes TaqMan. PCR was tested in a pilot 46 actual biopsy samples nodular basal cell carcinoma series. The sensitivity was placed with a detection limit of between 1 and 10 copies / μl. 50% (23/46) of the biopsies were positive for D. folliculorum. The specificity was 100% confirmed by sequencing. The technique shows good results for sensitivity and specificity that can make it useful as a tool for studies of cause and effect D. folliculorum and basal cell carcinoma.

  9. Viable neurons with luxury perfusion in hydrocephalus.

    PubMed

    Wong, C Y; Luciano, M G; MacIntyre, W J; Brunken, R C; Hahn, J F; Go, R T

    1997-09-01

    A woman with hydrocephalus due to aqueductal stenosis had functional imaging of cerebral perfusion and metabolism to demonstrate the effects of endoscopic third ventriculostomy--a new form of internal surgical shunting. Technetium-99m-ECD SPECT and 18F-FDG PET showed regional luxury perfusion at the left frontal region. Three months after a successful third ventriculostomy, a repeated imaging of cerebral perfusion and metabolism showed resolution of luxury perfusion and global improvement of both perfusion and metabolism. This concurred with postoperative clinical improvement. The paired imaging of cerebral perfusion and metabolism provides more information than just imaging perfusion or metabolism. Thus, the detection of perfusion and metabolism mismatch may open a new window of opportunity for surgical intervention.

  10. Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs

    SciTech Connect

    Kamiya, H.; McLaren, D.J.

    1987-02-01

    Compressed tissue autoradiography using (75Se)selenomethionine labelled parasites has been used to investigate the migration potential of normal and radiation attenuated cercariae of Schistosoma mansoni in naive guinea pigs. By Day 14 after infection. 44% of normal parasites were detected as reduced silver foci in the liver; this value corresponded well with the number of liver parasites recovered by retrograde perfusion of the hepatic portal system on Day 42 (42% of the challenge). In contrast, cercariae subjected to 50 krad of gamma irradiation failed to migrate out of the skin. The migration capacity of 20 krad irradiated parasites was less severely affected in that about half of the challenge parasites reached the lungs, but virtually none moved to the liver. These data are discussed in relation to the kinetics of immunity induced in guinea pigs by infection or vaccination with normal or radiation attenuated parasites.

  11. Malaria parasite clearance.

    PubMed

    White, Nicholas J

    2017-02-23

    Following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. Damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. Splenic clearance functions increase markedly in acute malaria. Either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of drug-damaged parasites is an important mechanism of clearance. The once-infected erythrocytes returned to the circulation have shortened survival. This contributes to post-artesunate haemolysis that may follow recovery in non-immune hyperparasitaemic patients. As the parasites mature Plasmodium vivax-infected erythrocytes become more deformable, whereas Plasmodium falciparum-infected erythrocytes become less deformable, but they escape splenic filtration by sequestering in venules and capillaries. Sequestered parasites are killed in situ by anti-malarial drugs and then disintegrate to be cleared by phagocytic leukocytes. After treatment with artemisinin derivatives some asexual parasites become temporarily dormant within their infected erythrocytes, and these may regrow after anti-malarial drug concentrations decline. Artemisinin resistance in P. falciparum reflects reduced ring stage susceptibility and manifests as slow parasite clearance. This is best assessed from the slope of the log-linear phase of parasitaemia reduction and is commonly measured as a parasite clearance half-life. Pharmacokinetic-pharmacodynamic modelling of anti-malarial drug effects on parasite clearance has proved useful in predicting therapeutic responses and in dose-optimization.

  12. Parasites: evolution's neurobiologists.

    PubMed

    Adamo, Shelley Anne

    2013-01-01

    For millions of years, parasites have altered the behaviour of their hosts. Parasites can affect host behaviour by: (1) interfering with the host's normal immune-neural communication, (2) secreting substances that directly alter neuronal activity via non-genomic mechanisms and (3) inducing genomic- and/or proteomic-based changes in the brain of the host. Changes in host behaviour are often restricted to particular behaviours, with many other behaviours remaining unaffected. Neuroscientists can produce this degree of selectivity by targeting specific brain areas. Parasites, however, do not selectively attack discrete brain areas. Parasites typically induce a variety of effects in several parts of the brain. Parasitic manipulation of host behaviour evolved within the context of the manipulation of other host physiological systems (especially the immune system) that was required for a parasite's survival. This starting point, coupled with the fortuitous nature of evolutionary innovation and evolutionary pressures to minimize the costs of parasitic manipulation, likely contributed to the complex and indirect nature of the mechanisms involved in host behavioural control. Because parasites and neuroscientists use different tactics to control behaviour, studying the methods used by parasites can provide novel insights into how nervous systems generate and regulate behaviour. Studying how parasites influence host behaviour will also help us integrate genomic, proteomic and neurophysiological perspectives on behaviour.

  13. [Parasitic factor and cancer].

    PubMed

    Khamidullin, R I; Aglullin, I R; Rakhmanin, Iu A; Pogorel'tsev, V I; Khamidullin, A R; Galkina, I V; Khamidullin, I R; Sultanaeva, E G

    2011-01-01

    There is opinion in the literature as to that liver trematode infections, such as opisthorchiasis, clonorchiasis, fascioliasis, and metorchiasis, can induce cancer of the liver pancreas, intestine - this all is clinically observed. The authors were the first in world practice to show the development of a hepatic blastomatous process in animals (albino rats, cats) with opisthorchiasis in 13%; cancer developed in 28 and 56% with the use of a hepatotropic carcinogen and combined (opisthorchiasis + a carcinogen) exposure, respectively. Throughout his life, a human being can easily catch these trematodes that have carcinogenic activity and these diseases concurrent with household and food carcinogens can give rise to tumors in the liver pancreas and intestine. Timely diagnosis and specific anthelmintic therapy are necessary to prevent parasitic cancer.

  14. Biological warfare: Microorganisms as drivers of host-parasite interactions.

    PubMed

    Dheilly, Nolwenn M; Poulin, Robert; Thomas, Frédéric

    2015-08-01

    Understanding parasite strategies for evasion, manipulation or exploitation of hosts is crucial for many fields, from ecology to medical sciences. Generally, research has focused on either the host response to parasitic infection, or the parasite virulence mechanisms. More recently, integrated studies of host-parasite interactions have allowed significant advances in theoretical and applied biology. However, these studies still provide a simplistic view of these as mere two-player interactions. Host and parasite are associated with a myriad of microorganisms that could benefit from the improved fitness of their partner. Illustrations of such complex multi-player interactions have emerged recently from studies performed in various taxa. In this conceptual article, we propose how these associated microorganisms may participate in the phenotypic alterations induced by parasites and hence in host-parasite interactions, from an ecological and evolutionary perspective. Host- and parasite-associated microorganisms may participate in the host-parasite interaction by interacting directly or indirectly with the other partner. As a result, parasites may develop (i) the disruptive strategy in which the parasite alters the host microbiota to its advantage, and (ii) the biological weapon strategy where the parasite-associated microorganism contributes to or modulates the parasite's virulence. Some phenotypic alterations induced by parasite may also arise from conflicts of interests between the host or parasite and its associated microorganism. For each situation, we review the literature and propose new directions for future research. Specifically, investigating the role of host- and parasite-associated microorganisms in host-parasite interactions at the individual, local and regional level will lead to a holistic understanding of how the co-evolution of the different partners influences how the other ones respond, both ecologically and evolutionary. The conceptual framework we

  15. Parasites and marine invasions: Ecological and evolutionary perspectives

    NASA Astrophysics Data System (ADS)

    Goedknegt, M. Anouk; Feis, Marieke E.; Wegner, K. Mathias; Luttikhuizen, Pieternella C.; Buschbaum, Christian; Camphuysen, Kees (C. J.); van der Meer, Jaap; Thieltges, David W.

    2016-07-01

    Worldwide, marine and coastal ecosystems are heavily invaded by introduced species and the potential role of parasites in the success and impact of marine invasions has been increasingly recognized. In this review, we link recent theoretical developments in invasion ecology with empirical studies from marine ecosystems in order to provide a conceptual framework for studying the role of parasites and their hosts in marine invasions. Based on an extensive literature search, we identified six mechanisms in which invaders directly or indirectly affect parasite and host populations and communities: I) invaders can lose some or all of their parasites during the invasion process (parasite release or reduction), often causing a competitive advantage over native species; II) invaders can also act as a host for native parasites, which may indirectly amplify the parasite load of native hosts (parasite spillback); III) invaders can also be parasites themselves and be introduced without needing co-introduction of the host (introduction of free-living infective stages); IV) alternatively, parasites may be introduced together with their hosts (parasite co-introduction with host); V) consequently, these co-introduced parasites can sometimes also infect native hosts (parasite spillover); and VI) invasive species may be neither a host nor a parasite, but nevertheless affect native parasite host interactions by interfering with parasite transmission (transmission interference). We discuss the ecological and evolutionary implications of each of these mechanisms and generally note several substantial effects on natural communities and ecosystems via i) mass mortalities of native populations creating strong selection gradients, ii) indirect changes in species interactions within communities and iii) trophic cascading and knock-on effects in food webs that may affect ecosystem function and services. Our review demonstrates a wide range of ecological and evolutionary implications of

  16. Cold Crystalloid Perfusion Provides Cardiac Preservation Superior to Cold Storage for Donation After Circulatory Death.

    PubMed

    Choong, Jonathan W; Ou, Ruchong; Lim, Yi Wee; Rosenfeldt, Franklin L

    2016-03-01

    We previously showed that donation after circulatory death (DCD) canine hearts can be resuscitated if perfused with warm blood. However, clinical application of this technique is complex and difficult. We have developed a simplified system of cold crystalloid perfusion and compared it with standard cold storage for DCD heart preservation. Anesthetized greyhounds underwent 30 minutes DCD by withdrawal of ventilation followed by assignment to either 4 hours of perfusion (n = 6) or cold storage (n = 7). Nonpreserved hearts (n = 5) served as a normal reference group. Perfusion hearts were reperfused with a protective solution then perfused for 4 hours with a novel oxygenated, nutrient-containing solution at 20 mL/min at 4°C to 10°C. Cold storage hearts were flushed with St Thomas' cardioplegic solution and stored in ice. After preservation, the recovery of the hearts was assessed on a blood-perfused working heart rig. During preservation, perfusion hearts consumed oxygen (0.09 ± 0.01 mL/100 g per minute) and showed decreasing lactate production in the perfusate (initial: 0.031 ± 0.004 vs final: 0.007 ± 0.002 mmol/min; P = 0.001). After preservation, compared to cold storage hearts, perfusion hearts had higher cardiac output (P = 0.004), LV dP/dt max (P = 0.003) and myocardial oxygen efficiency (P = 0.01), with lower blood perfusate lactate (P = 0.007). Hemodynamic values of perfused hearts reached 60% or more those in the normal reference group. Continuous cold crystalloid perfusion in a canine model of DCD: (1) facilitates aerobic metabolism and resuscitates the DCD heart, (2) provides functional and metabolic recovery superior to cold storage, (3) shows promise for improved clinical preservation of DCD and marginal donor hearts.

  17. Parasite and host assemblages: embracing the reality will improve our knowledge of parasite transmission and virulence

    PubMed Central

    Rigaud, Thierry; Perrot-Minnot, Marie-Jeanne; Brown, Mark J. F.

    2010-01-01

    Interactions involving several parasite species (multi-parasitized hosts) or several host species (multi-host parasites) are the rule in nature. Only a few studies have investigated these realistic, but complex, situations from an evolutionary perspective. Consequently, their impact on the evolution of parasite virulence and transmission remains poorly understood. The mechanisms by which multiple infections may influence virulence and transmission include the dynamics of intrahost competition, mediation by the host immune system and an increase in parasite genetic recombination. Theoretical investigations have yet to be conducted to determine which of these mechanisms are likely to be key factors in the evolution of virulence and transmission. In contrast, the relationship between multi-host parasites and parasite virulence and transmission has seen some theoretical investigation. The key factors in these models are the trade-off between virulence across different host species, variation in host species quality and patterns of transmission. The empirical studies on multi-host parasites suggest that interspecies transmission plays a central role in the evolution of virulence, but as yet no complete picture of the phenomena involved is available. Ultimately, determining how complex host–parasite interactions impact the evolution of host–parasite relationships will require the development of cross-disciplinary studies linking the ecology of quantitative networks with the evolution of virulence. PMID:20667874

  18. Magnetic resonance cardiac perfusion imaging-a clinical perspective.

    PubMed

    Hunold, Peter; Schlosser, Thomas; Barkhausen, Jörg

    2006-08-01

    Coronary artery disease (CAD) with its clinical appearance of stable or unstable angina and acute myocardial infarction is the leading cause of death in developed countries. In view of increasing costs and the rising number of CAD patients, there has been a major interest in reliable non-invasive imaging techniques to identify CAD in an early (i.e. asymptomatic) stage. Since myocardial perfusion deficits appear very early in the "ischemic cascade", a major breakthrough would be the non-invasive quantification of myocardial perfusion before functional impairment might be detected. Therefore, there is growing interest in other, target-organ-specific parameters, such as relative and absolute myocardial perfusion imaging. Magnetic resonance (MR) imaging has been proven to offer attractive concepts in this respect. However, some important difficulties have not been resolved so far, which still causes uncertainty and prevents the broad application of MR perfusion imaging in a clinical setting. This review explores recent technical developments in MR hardware, software and contrast agents, as well as their impact on the current and future clinical status of MR imaging of first-pass myocardial perfusion imaging.

  19. Transcriptome analyses reveal protein and domain families that delineate stage-related development in the economically important parasitic nematodes, Ostertagia ostertagi and Cooperia oncophora

    USDA-ARS?s Scientific Manuscript database

    Cooperia oncophora and Ostertagia ostertagi are among the most important gastrointestinal nematodes of cattle worldwide. The economic losses caused by these parasites are on the order of hundreds of millions of dollars per year. Conventional treatment of these parasites is through anthelmintic drug...

  20. A perfusion protocol for lizards, including a method for brain removal

    PubMed Central

    Hoops, Daniel

    2015-01-01

    The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. Perfusion achieves optimal fixation by pumping fixative directly through an animal’s circulatory system. Standard perfusion techniques were developed primarily for application in mammals, which are traditional neuroscience research models. Increasingly, other vertebrate groups are also being used in neuroscience. Following mammalian perfusion protocols for non-mammalian vertebrates often results in failed perfusions. Here, I present a modified perfusion protocol suitable for lizards. Though geared towards standard brain perfusion, this protocol is easily modified for the perfusion of other tissues and for various specialized histological techniques. • The two aortas of the lizard heart, emerging from a single ventricle, mean that care must be taken to place the perfusion needle in the correct aorta, unlike in mammals. • Only the head and neck perfuse – the visceral organs will not decolour, and the body may not twitch. • I also include a method for removing a lizard brain, which differs from mammals due to the incomplete and thicker skull of the lizard. PMID:26150986

  1. Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response.

    PubMed

    Khan, Imtiaz A; Moretto, Magali; Wei, Xiao-Qing; Williams, Martha; Schwartzman, Joseph D; Liew, Foo Y

    2002-06-03

    Interferon (IFN)-gamma-producing CD8+ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8+ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8+ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor alpha (sIL-15Ralpha) to block the host endogenous IL-15. The treatment markedly reduced the ability of the immune animals to control a lethal infection. CD8+ T cell activities in the sIL-15Ralpha-administered mice were severely reduced as determined by IFN-gamma release and target cell lysis assays. The loss of CD8+ T cell immunity due to sIL-15Ralpha treatment was further demonstrated by adoptive transfer experiments. Naive recipients transferred with CD44(hi) activated/memory CD8+ T cells and treated with sIL-15Ralpha failed to resist a lethal T. gondii infection. Moreover, sIL-15Ralpha treatment of the recipients blocked the ability of donor CD44(hi) activated/memory CD8+ T cells to replicate in response to T. gondii challenge. To our knowledge, this is the first demonstration of the important role of host IL-15 in the development of antigen-specific memory CD8+ T cells against an intracellular infection.

  2. Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th-1 host immune responses in the absence of parasite replication1

    PubMed Central

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2008-01-01

    A single inoculation of mice with the live attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hyper-virulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infection with cps1-1 elicits long-lasting CD8+ T cell mediated immunity. We show that immunization with cps1-1 infected DCs elicits long-lasting immunity. Intraperitoneal infection with cps1-1 induced a rapid influx of GR1+ neutrophils and 2 stages of GR1+ CD68+ inflammatory monocyte infiltration into the site of inoculation. CD19+ B cells and CD3+ T cells steadily increase for 8 days after infection. CD8+ T cells were rapidly recruited to the site of infection and increased faster than CD4+ T cells. Surprisingly, cps1-1 infection induced high systemic levels of bioactive IL-12p70 and very low level and transient systemic Ifn-γ. Furthermore, we show significant levels of these inflammatory cytokines were locally produced at the site of cps1-1 inoculation. These findings offer new insight into immunological mechanisms and local host responses to a non-replicating Type I parasite infection associated with development of long-lasting immunity to Toxoplasma gondii. PMID:19124750

  3. Development of in situ hybridization and PCR assays for the detection of Enterocytozoon hepatopenaei (EHP), a microsporidian parasite infecting penaeid shrimp.

    PubMed

    Tang, Kathy F J; Pantoja, Carlos R; Redman, Rita M; Han, Jee Eun; Tran, Loc H; Lightner, Donald V

    2015-09-01

    A microsporidian parasite, Enterocytozoon hepatopenaei (abbreviated as EHP), is an emerging pathogen for penaeid shrimp. EHP has been found in several shrimp farming countries in Asia including Vietnam, Thailand, Malaysia, Indonesia and China, and is reported to be associated with growth retardation in farmed shrimp. We examined the histological features from infected shrimp collected from Vietnam and Brunei, these include the presence of basophilic inclusions in the hepatopancreas tubule epithelial cells, in which EHP is found at various developmental stages, ranging from plasmodia to mature spores. By a PCR targeting the 18S rRNA gene, a 1.1kb 18S rRNA gene fragment of EHP was amplified, and this sequence showed a 100% identity to EHP found in Thailand and China. This fragment was cloned and labeled with digoxigenin-11-dUTP, and in situ hybridized to tissue sections of infected Penaeus vannamei (from Vietnam) and P. stylirostris (Brunei). The results of in situ hybridization were specific, the probe only reacted to the EHP within the cytoplasmic inclusions, not to a Pleistophora-like microsporidium that is associated with cotton shrimp disease. Subsequently, we developed a PCR assay from this 18S rRNA gene region, this PCR is shown to be specific to EHP, did not react to 2 other parasitic pathogens, an amoeba and the cotton shrimp disease microsporidium, nor to genomic DNA of various crustaceans including polychaetes, squids, crabs and krill. EHP was detected, through PCR, in hepatopancreatic tissue, feces and water sampled from infected shrimp tanks, and in some samples of Artemia biomass. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effect of cardiopulmonary bypass on gastrointestinal perfusion and function.

    PubMed

    Gaer, J A; Shaw, A D; Wild, R; Swift, R I; Munsch, C M; Smith, P L; Taylor, K M

    1994-02-01

    Gastric mucosal tonometry was used to determine the adequacy of gastrointestinal perfusion in 10 patients undergoing elective myocardial revascularization. Patients were prospectively randomized to receive either pulsatile or nonpulsatile flow during cardiopulmonary bypass. All patients showed a reduction in gastric mucosal perfusion during bypass, manifested by a reduction in the gastric mucosal pH, which occurred independently of variations in the arterial pH. In the group of patients receiving nonpulsatile flow, this reduction was significantly greater (p < 0.05). Cardiopulmonary bypass using nonpulsatile flow is associated with the development of a gastric mucosal acidosis, which may have implications for the development of postoperative complications.

  5. Perfusion decellularization of whole organs.

    PubMed

    Guyette, Jacques P; Gilpin, Sarah E; Charest, Jonathan M; Tapias, Luis F; Ren, Xi; Ott, Harald C

    2014-01-01

    The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo.

  6. Monitoring tissue perfusion, oxygenation, and metabolism in critically ill patients.

    PubMed

    Ekbal, Nasirul J; Dyson, Alex; Black, Claire; Singer, Mervyn

    2013-06-01

    Alterations in oxygen transport and use are integral to the development of multiple organ failure; therefore, the ultimate goal of resuscitation is to restore effective tissue oxygenation and cellular metabolism. Hemodynamic monitoring is the cornerstone of management to promptly identify and appropriately manage (impending) organ dysfunction. Prospective randomized trials have confirmed outcome benefit when preemptive or early treatment is directed toward maintaining or restoring adequate tissue perfusion. However, treatment end points remain controversial, in large part because of current difficulties in determining what constitutes "optimal." Information gained from global whole-body monitoring may not detect regional organ perfusion abnormalities until they are well advanced. Conversely, the ideal "canary" organ that is readily accessible for monitoring, yet offers an early and sensitive indicator of tissue "unwellness," remains to be firmly identified. This review describes techniques available for real-time monitoring of tissue perfusion and metabolism and highlights novel developments that may complement or even supersede current tools.

  7. Complete inhibition of creatine kinase in isolated perfused rat hearts

    SciTech Connect

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.

  8. Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites. 2. Altered vacuolar volume regulation in drug resistant malaria.

    PubMed

    Gligorijevic, Bojana; Bennett, Tyler; McAllister, Ryan; Urbach, Jeffrey S; Roepe, Paul D

    2006-10-17

    In the previous paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12400-12410], we reported on a customized Nipkow spinning disk confocal microscopy (SDCM) system and its initial application to DIC imaging of hemozoin within live, synchronized, intraerythrocytic Plasmodium falciparum malarial parasites. In this paper, we probe the biogenesis as well as the volume and pH regulation of the parasite digestive vacuole (DV), using the fluorescence imaging capabilities of the system. Several previous reports have suggested that mutant PfCRT protein, which causes chloroquine resistance (CQR) in P. falciparum, also causes increased acidification of the DV. Since pH and volume regulation are often linked, we wondered whether DV volume differences might be associated with CQR. Using fast acquisition of SDCM z stacks for synchronized parasites with OGd internalized into the DV, followed by iterative deconvolution using experimental point spread functions, we quantify the volume of the DV for live, intraerythrocytic HB3 (CQS), Dd2 (CQR via drug selection), GCO3 (CQS), and GCO3/C3(Dd2) (CQR via transfection with mutant pfcrt) malarial parasites as they develop within the human red blood cell. We find that relative to both CQS strains, both CQR strains show significantly increased DV volume as the organelle forms upon entry into the trophozoite stage of development and that this persists until the trophozoite-schizont boundary. A more acidic DV pH is found for CQR parasites as soon as the organelle forms and persists throughout the trophozoite stage. We probe DV volume and pH changes upon ATP depletion, hypo- and hypertonic shock, and rapid withdrawal of perfusate chloride. Taken together, these data suggest that the PfCRT mutations that cause CQR also lead to altered DV volume regulation.

  9. Intracellular Parasite Invasion Strategies

    NASA Astrophysics Data System (ADS)

    Sibley, L. D.

    2004-04-01

    Intracellular parasites use various strategies to invade cells and to subvert cellular signaling pathways and, thus, to gain a foothold against host defenses. Efficient cell entry, ability to exploit intracellular niches, and persistence make these parasites treacherous pathogens. Most intracellular parasites gain entry via host-mediated processes, but apicomplexans use a system of adhesion-based motility called ``gliding'' to actively penetrate host cells. Actin polymerization-dependent motility facilitates parasite migration across cellular barriers, enables dissemination within tissues, and powers invasion of host cells. Efficient invasion has brought widespread success to this group, which includes Toxoplasma, Plasmodium, and Cryptosporidium.

  10. Sphingolipids in parasitic protozoa

    PubMed Central

    Zhang, Kai; Bangs, James D.; Beverley, Stephen M.

    2009-01-01

    The surface of most protozoan parasites relies heavily upon lipid-anchored molecules, to form protective barriers and play critical functions required for infectivity. Sphingolipids (SLs) play important roles through their abundance and involvement in membrane microdomain formation, as well as serving as the lipid anchor for many of these molecules, and in some but possibly not all species, as important signaling molecules. Interactions of parasite sphingolipid metabolism with that of the host may potentially contribute to parasite survival and/or host defense. In this chapter we summarize current knowledge of SL structure, synthesis and function in several of the major parasitic protozoan groups. PMID:20919659

  11. Pharmacologic effects of a nitrate coronary vasodilator on cardiac perfusion and function, measured semiquantitatively

    SciTech Connect

    Winsor, D.W.; Winsor, T.; Krohn, B.G.; Bernett, J.R.

    1982-09-01

    Peritrate (pentaerythritol tetranitrate), a nitrate coronary vasodilator, was capable of significantly increasing perfusion and function in ischemic heart muscle. The A2 image-processing computer with software developed by Burow was used to evaluate regional perfusion and segmental wall motion in six patients with ischemic areas in the myocardium. These image-processing techniques were satisfactory for evaluation of ischemic heart muscle.

  12. MR spectroscopy and MR perfusion character of cerebral sparganosis: a case report

    PubMed Central

    Chiu, C-H; Chiou, T-L; Hsu, Y-H; Yen, P-S

    2010-01-01

    The authors report the case of a 46-year-old woman with cerebral sparganosis resulting from infection with a larva of Spirometra. Computed tomography and magnetic resonance imaging revealed a mass lesion with prominent perifocal oedema in the left parietal lobe. Advanced imaging pulse sequences, including MR spectroscopy and MR perfusion, were performed. During surgery for the removal of a granuloma, the parasite was discovered and excised. Following treatment, the patient's neurological deficits markedly improved. PMID:20139254

  13. Demographic and socio-economic factors affecting the physical development, haemoglobin and parasitic infection status of schoolchildren in Sanliurfa province, Turkey.

    PubMed

    Ulukanligil, M; Seyrek, A

    2004-03-01

    A cross-sectional population-based survey was undertaken to evaluate the relationship between nutritional status and parasitic infections of schoolchildren and demographic, socio-economic factors in Sanliurfa province, southern Turkey. Nine hundred and eight schoolchildren took part in the survey: 57.2% boys and 42.7% girls. The children's mean z scores were as follows: height for age-0.8 (+/-1.0) and weight for age-1.0 (+/-0.9). The mean haemoglobin concentration was 123 g/l (+/-2.1) and the prevalence of parasitic infections was 55.1%. In total, 50.2% of children were hungry when they arrived at school and 13.4% worked after school. Over 70% (70.4%) of mothers and 18.1% of fathers were illiterate, 16.1% of fathers were unemployed and 46.3% of fathers were engaged in low-income labour. The mean number of children in each family was 5.4 (+/-2.5), and the mean number of children from each family who attended school was 2.1 (+/-1.1). The school-attendance ratio was 0.4 (+/-1.0). Data indicated that older children had significantly lower mean z scores of height (P < 0.0001) and weight for age (P < 0.0001) than younger children, and boys had significantly lower mean z scores of height for age than girls (P < 0.0001). Children living in shantytown areas had significantly lower mean z scores of height for age (P < 0.0001) and weight for age (P < 0.0001), lower mean haemoglobin concentrations (P : 0.003)and a worse parasitic infection status (P < 0.0001) than those living in apartment areas. Children who were hungry when they arrived at school had significantly lower mean haemoglobin concentrations than those who had eaten (P : 0.04). Multiple regression analyses indicated that mean z scores of height for age were significantly related to maternal (multiple R = 0.183; P < 0.0001) and paternal illiteracy (multiple R = 0.216; P : 0.004). Mean z scores of weight for age were significantly related to maternal illiteracy (multiple R = 0.154; P < 0.0001), as was parasitic

  14. A life cycle database for parasitic acanthocephalans, cestodes, and nematodes.

    PubMed

    Benesh, Daniel P; Lafferty, Kevin D; Kuris, Armand

    2017-03-01

    Parasitologists have worked out many complex life cycles over the last ~150 yr, yet there have been few efforts to synthesize this information to facilitate comparisons among taxa. Most existing host-parasite databases focus on particular host taxa, do not distinguish final from intermediate hosts, and lack parasite life-history information. We summarized the known life cycles of trophically transmitted parasitic acanthocephalans, cestodes, and nematodes. For 973 parasite species, we gathered information from the literature on the hosts infected at each stage of the parasite life cycle (8,510 host-parasite species associations), what parasite stage is in each host, and whether parasites need to infect certain hosts to complete the life cycle. We also collected life-history data for these parasites at each life cycle stage, including 2,313 development time measurements and 7,660 body size measurements. The result is the most comprehensive data summary available for these parasite taxa. In addition to identifying gaps in our knowledge of parasite life cycles, these data can be used to test hypotheses about life cycle evolution, host specificity, parasite life-history strategies, and the roles of parasites in food webs.

  15. A life cycle database for parasitic acanthocephalans, cestodes, and nematodes

    USGS Publications Warehouse

    Benesh, Daniel P.; Lafferty, Kevin D.; Kuris, Armand

    2017-01-01

    Parasitologists have worked out many complex life cycles over the last ~150 years, yet there have been few efforts to synthesize this information to facilitate comparisons among taxa. Most existing host-parasite databases focus on particular host taxa, do not distinguish final from intermediate hosts, and lack parasite life-history information. We summarized the known life cycles of trophically transmitted parasitic acanthocephalans, cestodes, and nematodes. For 973 parasite species, we gathered information from the literature on the hosts infected at each stage of the parasite life cycle (8510 host-parasite species associations), what parasite stage is in each host, and whether parasites need to infect certain hosts to complete the life cycle. We also collected life-history data for these parasites at each life cycle stage, including 2313 development time measurements and 7660 body size measurements. The result is the most comprehensive data summary available for these parasite taxa. In addition to identifying gaps in our knowledge of parasite life cycles, these data can be used to test hypotheses about life cycle evolution, host specificity, parasite life-history strategies, and the roles of parasites in food webs.

  16. Mixed Infections and Hybridisation in Monogenean Parasites

    PubMed Central

    Schelkle, Bettina; Faria, Patricia J.; Johnson, Mireille B.; van Oosterhout, Cock; Cable, Joanne

    2012-01-01

    Theory predicts that sexual reproduction promotes disease invasion by increasing the evolutionary potential of the parasite, whereas asexual reproduction tends to enhance establishment success and population growth rate. Gyrodactylid monogeneans are ubiquitous ectoparasites of teleost fish, and the evolutionary success of the specious Gyrodactylus genus is thought to be partly due to their use of various modes of reproduction. Gyrodactylus turnbulli is a natural parasite of the guppy (Poecilia reticulata), a small, tropical fish used as a model for behavioural, ecological and evolutionary studies. Using experimental infections and a recently developed microsatellite marker, we conclusively show that monogenean parasites reproduce sexually. Conservatively, we estimate that sexual recombination occurs and that between 3.7–10.9% of the parasites in our experimental crosses are hybrid genotypes with ancestors from different laboratory strains of G. turnbulli. We also provide evidence of hybrid vigour and/or inter-strain competition, which appeared to lead to a higher maximum parasite load in mixed infections. Finally, we demonstrate inbreeding avoidance for the first time in platyhelminths which may influence the distribution of parasites within a host and their subsequent exposure to the host's localized immune response. Combined reproductive modes and inbreeding avoidance may explain the extreme evolutionary diversification success of parasites such as Gyrodactylus, where host-parasite coevolution is punctuated by relatively frequent host switching. PMID:22808040

  17. Mixed infections and hybridisation in monogenean parasites.

    PubMed

    Schelkle, Bettina; Faria, Patricia J; Johnson, Mireille B; van Oosterhout, Cock; Cable, Joanne

    2012-01-01

    Theory predicts that sexual reproduction promotes disease invasion by increasing the evolutionary potential of the parasite, whereas asexual reproduction tends to enhance establishment success and population growth rate. Gyrodactylid monogeneans are ubiquitous ectoparasites of teleost fish, and the evolutionary success of the specious Gyrodactylus genus is thought to be partly due to their use of various modes of reproduction. Gyrodactylus turnbulli is a natural parasite of the guppy (Poecilia reticulata), a small, tropical fish used as a model for behavioural, ecological and evolutionary studies. Using experimental infections and a recently developed microsatellite marker, we conclusively show that monogenean parasites reproduce sexually. Conservatively, we estimate that sexual recombination occurs and that between 3.7-10.9% of the parasites in our experimental crosses are hybrid genotypes with ancestors from different laboratory strains of G. turnbulli. We also provide evidence of hybrid vigour and/or inter-strain competition, which appeared to lead to a higher maximum parasite load in mixed infections. Finally, we demonstrate inbreeding avoidance for the first time in platyhelminths which may influence the distribution of parasites within a host and their subsequent exposure to the host's localized immune response. Combined reproductive modes and inbreeding avoidance may explain the extreme evolutionary diversification success of parasites such as Gyrodactylus, where host-parasite coevolution is punctuated by relatively frequent host switching.

  18. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  19. Perfusion studies in cholera: methods and procedures.

    PubMed

    van Loon, F P; Gyr, K; Banik, A K

    1992-09-01

    This paper reviews the characteristics of perfusion techniques in the study of intestinal functions by specifically examining the methods and procedures of perfusion in patients with diarrhoea due to infection with V. cholerae 01. Because of abundant jejunal secretion of water and electrolytes in cholera, perfusion studies require special approaches with regard to patient preparation, use of tubing material, selection of markers, and rate of perfusion. A discussion on specific problems involved in marker perfusion techniques in cholera and on the interpretation of the results is followed by practical recommendations.

  20. Perfused multiwell plate for 3D liver tissue engineering.

    PubMed

    Domansky, Karel; Inman, Walker; Serdy, James; Dash, Ajit; Lim, Matthew H M; Griffith, Linda G

    2010-01-07

    In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days of culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers.

  1. Modelling of temperature and perfusion during scalp cooling.

    PubMed

    Janssen, F E M; Van Leeuwen, G M J; Van Steenhoven, A A

    2005-09-07

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 degrees C to 18.3 degrees C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 degrees C to 21.8 degrees C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  2. Perfused Multiwell Plate for 3D Liver Tissue Engineering

    PubMed Central

    Domansky, Karel; Inman, Walker; Serdy, James; Dash, Ajit; Lim, Matthew H. M.

    2014-01-01

    In vitro models that capture the complexity of in vivo tissue and organ behaviors in a scalable and easy-to-use format are desirable for drug discovery. To address this, we have developed a bioreactor that fosters maintenance of 3D tissue cultures under constant perfusion and we have integrated multiple bioreactors into an array in a multiwell plate format. All bioreactors are fluidically isolated from each other. Each bioreactor in the array contains a scaffold that supports formation of hundreds of 3D microscale tissue units. The tissue units are perfused with cell culture medium circulated within the bioreactor by integrated pneumatic diaphragm micropumps. Electronic controls for the pumps are kept outside the incubator and connected to the perfused multiwell by pneumatic lines. The docking design and open-well bioreactor layout make handling perfused multiwell plates similar to using standard multiwell tissue culture plates. A model of oxygen consumption and transport in the circulating culture medium was used to predict appropriate operating parameters for primary liver cultures. Oxygen concentrations at key locations in the system were then measured as a function of flow rate and time after initiation of culture to determine oxygen consumption rates. After seven days in culture, tissue formed from cells seeded in the perfused multiwell reactor remained functionally viable as assessed by immunostaining for hepatocyte and liver sinusoidal endothelial cell (LSEC) phenotypic markers. PMID:20024050

  3. Real-time vascular mechanosensation through ex vivo artery perfusion

    PubMed Central

    2014-01-01

    Background Cell-based perfusion studies have provided great insight into fluid-sensing mechanisms, such as primary cilia in the renal and vascular systems. However, the intrinsic limitations of in vitro cell culture, such as the inability to reflect cellular organization within tissues, has distanced observed paradigms from possible clinical developments. Here we describe a protocol that applies ex vivo artery perfusion and calcium imaging to observe real-time cellular responses to fluid-shear stress. Results Through our ex vivo artery perfusion method, we were able to simulate physiological flow and initiate distinct fluid shear stress mechanosensory responses, as well as induced acetylcholine responses in mouse aortic tissue. The observed calcium profiles confirm results found through previous in vitro cell culture experiments. The overall procedure, including dissection, sample preparation and perfusion, takes around 3 hours to complete. Conclusion Through our unique method, we are able to induce laminar flow within intact mouse aortic tissue and illicit subsequent cellular responses. This method of ex vivo artery perfusion provides the opportunity to bridge the novel findings of in vitro studies with subsequent physiological models of fluid-shear stress mechanosensation in vascular tissues. PMID:24685068

  4. Modelling of temperature and perfusion during scalp cooling

    NASA Astrophysics Data System (ADS)

    Janssen, F. E. M.; Van Leeuwen, G. M. J.; Van Steenhoven, A. A.

    2005-09-01

    Hair loss is a feared side effect of chemotherapy treatment. It may be prevented by cooling the scalp during administration of cytostatics. The supposed mechanism is that by cooling the scalp, both temperature and perfusion are diminished, affecting drug supply and drug uptake in the hair follicle. However, the effect of scalp cooling varies strongly. To gain more insight into the effect of cooling, a computer model has been developed that describes heat transfer in the human head during scalp cooling. Of main interest in this study are the mutual influences of scalp temperature and perfusion during cooling. Results of the standard head model show that the temperature of the scalp skin is reduced from 34.4 °C to 18.3 °C, reducing tissue blood flow to 25%. Based upon variations in both thermal properties and head anatomies found in the literature, a parameter study was performed. The results of this parameter study show that the most important parameters affecting both temperature and perfusion are the perfusion coefficient Q10 and the thermal resistances of both the fat and the hair layer. The variations in the parameter study led to skin temperature ranging from 10.1 °C to 21.8 °C, which in turn reduced relative perfusion to 13% and 33%, respectively.

  5. Mortality and pathology in birds due to Plasmodium (Giovannolaia) homocircumflexum infection, with emphasis on the exoerythrocytic development of avian malaria parasites.

    PubMed

    Ilgūnas, Mikas; Bukauskaitė, Dovilė; Palinauskas, Vaidas; Iezhova, Tatjana A; Dinhopl, Nora; Nedorost, Nora; Weissenbacher-Lang, Christiane; Weissenböck, Herbert; Valkiūnas, Gediminas

    2016-05-04

    Species of avian malaria parasites (Plasmodium) are widespread, but their virulence has been insufficiently investigated, particularly in wild birds. During avian malaria, several cycles of tissue merogony occur, and many Plasmodium spp. produce secondary exoerythrocytic meronts (phanerozoites), which are induced by merozoites developing in erythrocytic meronts. Phanerozoites markedly damage organs, but remain insufficiently investigated in the majority of described Plasmodium spp. Avian malaria parasite Plasmodium (Giovannolaia) homocircumflexum (lineage pCOLL4) is virulent and produces phanerozoites in domestic canaries Serinus canaria, but its pathogenicity in wild birds remains unknown. The aim of this study was to investigate the pathology caused by this infection in species of common European birds. One individual of Eurasian siskin Carduelis spinus, common crossbill Loxia curvirostra and common starling Sturnus vulgaris were exposed to P. homocircumflexum infection by intramuscular sub-inoculation of infected blood. The birds were maintained in captivity and parasitaemia was monitored until their death due to malaria. Brain, heart, lungs, liver, spleen, kidney, and a piece of breast muscle were examined using histology and chromogenic in situ hybridization (ISH) methods. All exposed birds developed malaria infection, survived the peak of parasitaemia, but suddenly died between 30 and 38 days post exposure when parasitaemia markedly decreased. Numerous phanerozoites were visible in histological sections of all organs and were particularly easily visualized after ISH processing. Blockage of brain capillaries with phanerozoites may have led to cerebral ischaemia, causing cerebral paralysis and is most likely the main reason of sudden death of all infected individuals. Inflammatory response was not visible around the brain, heart and muscle phanerozoites, and it was mild in parenchymal organs. The endothelial damage likely causes dysfunction and failure of

  6. New mechanisms of disease and parasite-host interactions.

    PubMed

    de Souza, Tiago Alves Jorge; de Carli, Gabriel Jose; Pereira, Tiago Campos

    2016-09-01

    An unconventional interaction between a patient and parasites was recently reported, in which parasitic cells invaded host's tissues, establishing several tumors. This finding raises various intriguing hypotheses on unpredicted forms of interplay between a patient and infecting parasites. Here we present four unusual hypothetical host-parasite scenarios with intriguing medical consequences. Relatively simple experimental designs are described in order to evaluate such hypotheses. The first one refers to the possibility of metabolic disorders in parasites intoxicating the host. The second one is on possibility of patients with inborn errors of metabolism (IEM) being more resistant to parasites (due to accumulation of toxic compounds in the bloodstream). The third one refers to a mirrored scenario: development of tumors in parasites due to ingestion of host's circulating cancer cells. The last one describes a complex relationship between parasites accumulating a metabolite and supplying it to a patient with an IEM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Does moving up a food chain increase aggregation in parasites?

    PubMed Central

    Lester, R. J. G.

    2016-01-01

    General laws in ecological parasitology are scarce. Here, we evaluate data on numbers of fish parasites published by over 200 authors to determine whether acquiring parasites via prey is associated with an increase in parasite aggregation. Parasite species were grouped taxonomically to produce 20 or more data points per group as far as possible. Most parasites that remained at one trophic level were less aggregated than those that had passed up a food chain. We use a stochastic model to show that high parasite aggregation in predators can be solely the result of the accumulation of parasites in their prey. The model is further developed to show that a change in the predators feeding behaviour with age may further increase parasite aggregation. PMID:27170651

  8. Implications of bioactive solute transfer from hosts to parasitic plants.

    PubMed

    Smith, Jason D; Mescher, Mark C; De Moraes, Consuelo M

    2013-08-01

    Parasitic plants--which make their living by extracting nutrients and other resources from other plants--are important components of many natural ecosystems; and some parasitic species are also devastating agricultural pests. To date, most research on plant parasitism has focused on nutrient transfer from host to parasite and the impacts of parasites on host plants. Far less work has addressed potential effects of the translocation of bioactive non-nutrient solutes-such as phytohormones, secondary metabolites, RNAs, and proteins-on the development and physiology of parasitic plants and on their subsequent interactions with other organisms such as insect herbivores. A growing number of recent studies document the transfer of such molecules from hosts to parasites and suggest that they may have significant impacts on parasite physiology and ecology. We review this literature and discuss potential implications for management and priorities for future research.

  9. The pediatric template of brain perfusion

    PubMed Central

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  10. The pediatric template of brain perfusion.

    PubMed

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7-18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

  11. Water-Related Parasitic Diseases in China

    PubMed Central

    Lv, Shan; Tian, Li-Guang; Liu, Qin; Qian, Men-Bao; Fu, Qing; Steinmann, Peter; Chen, Jia-Xu; Yang, Guo-Jing; Yang, Kun; Zhou, Xiao-Nong

    2013-01-01

    Water-related parasitic diseases are directly dependent on water bodies for their spread or as a habitat for indispensable intermediate or final hosts. Along with socioeconomic development and improvement of sanitation, overall prevalence is declining in the China. However, the heterogeneity in economic development and the inequity of access to public services result in considerable burden due to parasitic diseases in certain areas and populations across the country. In this review, we demonstrated three aspects of ten major water-related parasitic diseases, i.e., the biology and pathogenicity, epidemiology and recent advances in research in China. General measures for diseases control and special control strategies are summarized. PMID:23685826

  12. Importance of organ preservation solution composition in reducing myocardial edema during machine perfusion for heart transplantation.

    PubMed

    Cobert, M L; Peltz, M; West, L M; Jessen, M E

    2010-06-01

    Machine perfusion preservation has been used experimentally to extend the storage interval of donor hearts. We previously demonstrated that machine perfusion with glucose-supplemented Celsior preservation solution led to superior reperfusion function but resulted in increased myocardial edema compared with conventional static preservation. We hypothesized that other solutions that contain an oncotic agent, such as University of Wisconsin Machine Perfusion Solution (UWMPS), might reduce graft edema development while maintaining myocardial oxidative metabolism during long-term storage. Canine hearts were stored and perfused in a perfusion preservation device (LifeCradle; Organ Transport Systems) after cardioplegic arrest and donor cardiectomy. Hearts were perfused either with glucose-supplemented Celsior (which lacks an oncotic agent) or UWMPS (which contains hydroxyethyl starch) at 5 degrees C in the perfusion device over 10 hours. Oxygen consumption (MVO(2)), lactate accumulation, regional flow distribution, and myocardial water content were measured. Hearts in both groups continued to extract oxygen over the entire perfusion interval. Lactate accumulation was minimal in both groups. Both solutions delivered perfusate evenly to all regions of myocardium. Heart weight increase (Celsior 31.3 +/- 4.3%, UWMPS -3.3 +/- 1.9%) and final myocardial water content (Celsior 80.2 +/- 1.3%, UWMPS 75.9 +/- 0.3%) were higher in the Celsior group (P < .005). Donor hearts can be supported by a perfusion device over relatively extended storage intervals. These organs continue to undergo oxidative metabolism with little lactate accumulation. An oncotic agent appears to be important in limiting increases in myocardial water content. UWMPS appears to be superior for perfusion preservation of myocardium by reducing edema development during storage.

  13. Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

    PubMed

    Halsøy, Kathrine; Kondratiev, Timofey; Tveita, Torkjel; Bjertnaes, Lars J

    2016-01-01

    Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the

  14. Systems analysis of host-parasite interactions.

    PubMed

    Swann, Justine; Jamshidi, Neema; Lewis, Nathan E; Winzeler, Elizabeth A

    2015-01-01

    Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies.

  15. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  16. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  17. Antimicrobial peptide action on parasites.

    PubMed

    Torrent, Marc; Pulido, David; Rivas, Luis; Andreu, David

    2012-08-01

    Diseases caused by protozoan parasites can pose a severe thread to human health and are behind some serious neglected tropical diseases like malaria and leishmaniasis. Though several different drugs have been developed in order to eradicate these diseases, a successful candidate has not yet been discovered. Among the most active compounds tested, antimicrobial peptides (AMPs) are particularly appealing because of their wide spectrum of action. AMPs have been described to perturb protozoan homeostasis by disrupting the cellular membranes but also by interfering with key processes in the parasite metabolism. In this review we describe the diverse mechanisms of action of AMPs on protozoan targets and how they can be exploited to treat diseases. Moreover, we describe with detail the antimicrobial action of AMPs on two major parasitical infections: leishmaniasis and malaria. All the features reviewed here show that AMPs are promising drugs to target protozoan parasites and that further understanding of the mechanism of action of these compounds will lead to improved drugs that could be worth to test in a clinical phase.

  18. Pets and Parasites

    MedlinePlus

    ... in Children and TeensRead MoreBMI Calculator Cat and Dog BitesApril 2017September 2000Pets and Animalsfamilydoctor.org editorial staffCat- ... and Parasites Share Print Pets and Parasites A dog may be man’s best friend. However, household pets ...

  19. PARASITES OF FISH

    EPA Science Inventory

    The intent of this chapter is to describe the parasites of importance to fishes maintained and used in laboratory settings. In contrast to the frist edition, the focus will be only on those parasites that pose a serious threat to or are common in fishes held in these confined en...

  20. PARASITES OF FISH

    EPA Science Inventory

    The intent of this chapter is to describe the parasites of importance to fishes maintained and used in laboratory settings. In contrast to the frist edition, the focus will be only on those parasites that pose a serious threat to or are common in fishes held in these confined en...

  1. Parasites and marine invasions

    USGS Publications Warehouse

    Torchin, M.E.; Lafferty, K.D.; Kuris, A.M.

    2002-01-01

    Introduced marine species are a major environmental and economic problem. The rate of these biological invasions has substantially increased in recent years due to the globalization of the world's economies. The damage caused by invasive species is often a result of the higher densities and larger sizes they attain compared to where they are native. A prominent hypothesis explaining the success of introduced species is that they are relatively free of the effects of natural enemies. Most notably, they may encounter fewer parasites in their introduced range compared to their native range. Parasites are ubiquitous and pervasive in marine systems, yet their role in marine invasions is relatively unexplored. Although data on parasites of marine organisms exist, the extent to which parasites can mediate marine invasions, or the extent to which invasive parasites and pathogens are responsible for infecting or potentially decimating native marine species have not been examined. In this review, we present a theoretical framework to model invasion success and examine the evidence for a relationship between parasite presence and the success of introduced marine species. For this, we compare the prevalence and species richness of parasites in several introduced populations of marine species with populations where they are native. We also discuss the potential impacts of introduced marine parasites on native ecosystems.

  2. Pancreas tumor model in rabbit imaged by perfusion CT scans

    NASA Astrophysics Data System (ADS)

    Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.

    2013-03-01

    The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.

  3. Myocardial perfusion scintigraphy: techniques, interpretation, indications and reporting.

    PubMed

    Fathala, Ahmed

    2011-01-01

    Myocardial perfusion single photon emission-computed tomography (MPS) has been one of the most important and common non-invasive diagnostic cardiac test. Gated MPS provides simultaneous assessment of myocardial perfusion and function with only one study. With appropriate attention to the MPS techniques, appropriate clinical utilization and effective reporting, gated MPS will remain a useful diagnostic test for many years to come. The aim of this article is to review the basic techniques of MPS, a simplified systematic approach for study interpretation, current clinical indications and reporting. After reading this article the reader should develop an understanding of the techniques, interpretation, current clinical indications and reporting of MPS studies.

  4. Review of laser speckle contrast techniques for visualizing tissue perfusion.

    PubMed

    Draijer, Matthijs; Hondebrink, Erwin; van Leeuwen, Ton; Steenbergen, Wiendelt

    2009-07-01

    When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.

  5. Vascular Tissue Engineering: Building Perfusable Vasculature for Implantation

    PubMed Central

    Gui, Liqiong; Niklason, Laura E.

    2014-01-01

    Tissue and organ replacement is required when there are no alternative therapies available. Although vascular tissue engineering was originally developed to meet the clinical demands of small-diameter vascular conduits as bypass grafts, it has evolved into a highly advanced field where perfusable vasculatures are generated for implantation. Herein, we review several cutting-edge techniques that have led to implantable human blood vessels in clinical trials, the novel approaches that build complex perfusable microvascular networks in functional tissues, the use of stem cells to generate endothelial cells for vascularization, as well as the challenges in bringing vascular tissue engineering technologies into the clinics. PMID:24533306

  6. Construction and validation of a microprocessor controlled extracorporal circuit in rats for the optimization of isolated limb perfusion.

    PubMed

    Gürtler, Ulrich; Fuchs, Peter; Stangelmayer, Achim; Bernhardt, Günther; Buschauer, Armin; Spruss, Thilo

    2004-12-01

    Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

  7. It's a predator-eat-parasite world: how characteristics of predator, parasite and environment affect consumption.

    PubMed

    Orlofske, Sarah A; Jadin, Robert C; Johnson, Pieter T J

    2015-06-01

    Understanding the effects of predation on disease dynamics is increasingly important in light of the role ecological communities can play in host-parasite interactions. Surprisingly, however, few studies have characterized direct predation of parasites. Here we used an experimental approach to show that consumption of free-living parasite stages is highly context dependent, with significant influences of parasite size, predator size and foraging mode, as well as environmental condition. Among the four species of larval trematodes and two types of predators (fish and larval damselflies) studied here, parasites with larger infective stages (size >1,000 μm) were most vulnerable to predation by fish, while small-bodied fish and damselflies (size <10 mm) consumed the most infectious stages. Small parasite species (size approx. 500 μm) were less frequently consumed by both fish and larval damselflies. However, these results depended strongly on light availability; trials conducted in the dark led to significantly fewer parasites consumed overall, especially those with a size of <1,000 μm, emphasizing the importance of circadian shedding times of parasite free-living stages for predation risk. Intriguingly, active predation functioned to help limit fishes' infection by directly penetrating parasite species. Our results are consistent with established theory developed for predation on zooplankton that emphasizes the roles of body size, visibility and predation modes and further suggest that consumer-resource theory may provide a predictive framework for when predators should significantly influence parasite transmission. These results contribute to our understanding of transmission in natural systems, the role of predator-parasite links in food webs and the evolution of parasite morphology and behavior.

  8. Superimposed display of coronary artery on gated myocardial perfusion scintigraphy.

    PubMed

    Nishimura, Yoshihiro; Fukuchi, Kazuki; Katafuchi, Tetsuro; Sagou, Masayoshi; Oka, Hisashi; Ishida, Yoshio; Murase, Kenya

    2004-09-01

    Fusion of images of vascular anatomy and of myocardial perfusion images might be helpful for understanding the relationship between ischemia and the responsible vessels. The aim of this study was to develop a simple means of superimposing the images obtained from coronary angiography and gated myocardial perfusion SPECT. Right and left oblique views from conventional coronary angiography and left ventriculography (LVG) were stored as 512 x 512 x 8-bit digital datasets and combined. We reconstructed images from routine gated myocardial perfusion imaging (MPI) by using (99m)Tc-tetrofosmin to match the oblique positions between the image from MPI and combined angiographic images. We then generated a 3-dimensional (3D) surface map by using the quantitative gated SPECT (QGS)/quantitative perfusion SPECT (QPS) program. Both the combined angiographic images and the 3D surface map were rescaled and unified by registering the internal landmarks between the 2 images. After subtraction of the LVG image, the coronary angiogram and the 3D surface map were fused into 1 image. All processes were performed with the QGS/QPS program and commercially available graphic software. We applied this method to datasets from a cardiac phantom and from several patients with coronary artery disease. In the phantom study, our technique could obtain a 3D surface map in which the oblique angle was identified as that of radiography and could realize image registration and superimposition of radiography on scintigraphy. The preliminary results from the patients indicated that the markedly stenotic vessels showed good coincidence with the regional myocardial perfusion abnormalities on the unified images. In addition, these images could show the relationship between the coronary artery and regional wall motion in the gated mode. We developed a simple method of superimposing the image of the coronary artery tree on images from gated MPI. The technique yielded useful information about myocardial

  9. Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

    PubMed

    Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2017-02-01

    Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

  10. Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development

    PubMed Central

    Moon, Robert W.; Whalley, David; Bowyer, Paul W.; Wallace, Claire; Rochani, Ankit; Nageshan, Rishi K.; Howell, Steven A.; Grainger, Munira; Jones, Hayley M.; Ansell, Keith H.; Chapman, Timothy M.; Taylor, Debra L.; Osborne, Simon A.; Baker, David A.; Tatu, Utpal

    2015-01-01

    Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in the trophozoite stage, indicating different modes of action for the two classes. The compounds also inhibited cyclic GMP (cGMP)-dependent protein kinase (PKG), and their potency against this enzyme was greatly reduced by substitution of the enzyme's gatekeeper residue at the ATP binding site. The effectiveness of the class 1 compounds against a parasite line expressing the modified PKG was also substantially reduced, suggesting that these compounds kill the parasite primarily through inhibition of PKG rather than CDPK1. HSP90 was identified as a binding partner of class 2 compounds, and a representative compound bound to the ATP binding site in the N-terminal domain of HSP90. Reducing the size of the gatekeeper residue of CDPK1 enabled inhibition of the enzyme by bumped kinase inhibitors; however, a parasite line expressing the modified enzyme showed no change in sensitivity to these compounds. Taken together, these findings suggest that CDPK1 may not be a suitable target for further inhibitor development and that the primary mechanism through which the imidazopyridazines kill parasites is by inhibition of PKG or HSP90. PMID:26711771

  11. Graphene oxide inhibits malaria parasite invasion and delays parasitic growth in vitro.

    PubMed

    Kenry; Lim, Ying Bena; Nai, Mui Hoon; Cao, Jianshu; Loh, Kian Ping; Lim, Chwee Teck

    2017-09-28

    The interactions between graphene oxide (GO) and various biological entities have been actively investigated in recent years, resulting in numerous potential bioapplications of these nanomaterials. Despite this, the biological interactions between GO and disease-causing protozoan parasites have not been well elucidated and remain relatively unexplored. Here, we investigate the in vitro interactions between GO nanosheets and a particular species of malaria parasites, Plasmodium falciparum (P. falciparum). We hypothesize that GO nanosheets may exhibit antimalarial characteristic via action mechanisms of physical obstruction of P. falciparum parasites as well as nutrient depletion. To ascertain this, we characterize the physical interactions between GO nanosheets, red blood cells (RBCs), and malarial parasites as well as the adsorption of several biomolecules necessary for parasitic survival and growth on GO nanosheets. Subsequent to establishing the origin of this antimalarial behavior of GO nanosheets, their efficiency in inhibiting parasite invasion is evaluated. We observe that GO nanosheets at various tested concentrations significantly inhibit the invasion of malaria parasites into RBCs. Furthermore, GO nanosheets delay parasite progression from the ring to the trophozoite stage. Overall, this study may further shed light on the graphene-parasite interactions and potentially facilitate the development of nanomaterial-based strategies for combating malaria.

  12. Parasites in cultured and feral fish.

    PubMed

    Scholz, T

    1999-08-01

    Parasites, causing little apparent damage in feral fish populations, may become causative agents of diseases of great importance in farmed fish, leading to pathological changes, decrease of fitness or reduction of the market value of fish. Despite considerable progress in fish parasitology in the last decades, major gaps still exist in the knowledge of taxonomy, biology, epizootiology and control of fish parasites, including such 'evergreens' as the ciliate Ichthyophthirius multifiliis, a causative agent of white spot disease, or proliferative kidney disease (PKD), one of the most economically damaging diseases in the rainbow trout industry which causative agent remain enigmatic. Besides long-recognized parasites, other potentially severe pathogens have appeared quite recently such as amphizoic amoebae, causative agents of amoebic gill disease (AGD), the monogenean Gyrodactylus salaris which has destroyed salmon populations in Norway, or sea lice, in particular Lepeophtheirus salmonis that endanger marine salmonids in some areas. Recent spreading of some parasites throughout the world (e.g. the cestode Bothriocephalus acheilognathi) has been facilitated through insufficient veterinary control during import of fish. Control of many important parasitic diseases is still far from being satisfactory and further research is needed. Use of chemotherapy has limitations and new effective, but environmentally safe drugs should be developed. A very promising area of future research seems to be studies on immunity in parasitic infections, use of molecular technology in diagnostics and development of new vaccines against the most pathogenic parasites.

  13. Immunogene and viral transcript dynamics during parasitic Varroa destructor mite infection of developing honey bee (Apis mellifera) pupae.

    PubMed

    Kuster, Ryan D; Boncristiani, Humberto F; Rueppell, Olav

    2014-05-15

    The ectoparasitic Varroa destructor mite is a major contributor to the ongoing honey bee health crisis. Varroa interacts with honey bee viruses, exacerbating their pathogenicity. In addition to vectoring viruses, immunosuppression of the developing honey bee hosts by Varroa has been proposed to explain the synergy between viruses and mites. However, the evidence for honey bee immune suppression by V. destructor is contentious. We systematically studied the quantitative effects of experimentally introduced V. destructor mites on immune gene expression at five specific time points during the development of the honey bee hosts. Mites reproduced normally and were associated with increased titers of deformed wing virus in the developing bees. Our data on different immune genes show little evidence for immunosuppression of honey bees by V. destructor. Experimental wounding of developing bees increases relative immune gene expression and deformed wing virus titers. Combined, these results suggest that mite feeding activity itself and not immunosuppression may contribute to the synergy between viruses and mites. However, our results also suggest that increased expression of honey bee immune genes decreases mite reproductive success, which may be explored to enhance mite control strategies. Finally, our expression data for multiple immune genes across developmental time and different experimental treatments indicates co-regulation of several of these genes and thus improves our understanding of the understudied honey bee immune system.

  14. House and stable fly (Diptera: Muscidae) seasonal abundance, larval development substrates, and natural parasitism on small equine farms in Florida

    USDA-ARS?s Scientific Manuscript database

    This 1-year study was designed to determine adult fly population levels and development substrates on four small equine farms. Results showed that pest flies were present year-round, but differences existed in population levels among farms and seasons. Fly larvae were not found on two of the farms, ...

  15. One Health: parasites and beyond.

    PubMed

    Blake, Damer P; Betson, Martha

    2017-01-01

    ://www.bsp.uk.net/home/) was focused on One Health, running under the title 'One Health: parasites and beyond…'. The meeting, held at the Royal Veterinary College (RVC) in Camden, London from September 14th to 15th, drew upon a blend of specialist parasitology reinforced with additional complementary expertise. Scientists, advocates, policy makers and industry representatives were invited to present at the meeting, promoting and developing One Health understanding with relevance to parasitology. The decision to widen the scope of the meeting to non-parasitological, but informative topics, is reflected in the diversity of the articles included in this special issue. A key feature of the meeting was encouragement of early career scientists, with more than 35% of the delegates registered as students and 25 posters.

  16. Emerging parasitic diseases of sheep.

    PubMed

    Taylor, M A

    2012-09-30

    There have been changes in the emergence and inability to control of a number of sheep parasitic infections over the last decade. This review focuses on the more globally important sheep parasites, whose reported changes in epidemiology, occurrence or failure to control are becoming increasingly evident. One of the main perceived driving forces is climate change, which can have profound effects on parasite epidemiology, especially for those parasitic diseases where weather has a direct effect on the development of free-living stages. The emergence of anthelmintic-resistant strains of parasitic nematodes and the increasing reliance placed on anthelmintics for their control, can exert profound changes on the epidemiology of those nematodes causing parasitic gastroenteritis. As a consequence, the effectiveness of existing control strategies presents a major threat to sheep production in many areas around the world. The incidence of the liver fluke, Fasciola hepatica, is inextricably linked to high rainfall and is particularly prevalent in high rainfall years. Over the last few decades, there have also been increasing reports of other fluke associated diseases, such as dicroceliosis and paramphistomosis, in a number of western European countries, possibly introduced through animal movements, and able to establish with changing climates. External parasite infections, such as myiasis, can cause significant economic loss and presents as a major welfare problem. The range of elevated temperatures predicted by current climate change scenarios, result in an elongated blowfly season with earlier spring emergence and a higher cumulative incidence of fly strike. Additionally, legislative decisions leading to enforced changes in pesticide usage and choices have resulted in increased reports and spread of ectoparasitic infections, particularly mite, lice and tick infestations in sheep. Factors, such as dip disposal and associated environmental concerns, and, perhaps more

  17. Radiographing puparia of tachinid parasites of the gypsy moth, and application in parasite-release programs

    Treesearch

    T. M. Odell; P. A. Godwin; W. B. White

    1974-01-01

    A radiographic technique has been developed for observing and quantifying development and mortality of Blepharipa scutellata ( Robineau-Desvoidy), Parasetigena agilis (Robineau-Desvoidy), and Compsilura concinnata (Meigen), tachinid parasites of the gypsy moth, Porthetria dispar (L.). Puparia...

  18. Intestinal perfusion monitoring using photoplethysmography

    NASA Astrophysics Data System (ADS)

    Akl, Tony J.; Wilson, Mark A.; Ericson, M. Nance; Coté, Gerard L.

    2013-08-01

    In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.

  19. Northward invasion of the parasitic deer ked ( Lipoptena cervi), is there geographical variation in pupal size and development duration?

    PubMed

    Kaunisto, Sirpa; Härkönen, Laura; Niemelä, Pekka; Roininen, Heikki; Ylönen, Hannu

    2011-03-01

    The deer ked (Lipoptena cervi) is a common ectoparasite of cervids. During the last decades the species has rapidly invaded in northern Europe, especially in Finland, towards the north and increased its prevalence on the moose population. Consequently, during this rapid invasion the deer ked has faced more severe climatic conditions. We studied whether pupal size (measured as pupal weight) and pupal development duration of the deer ked varies along historical invasion zones and temperature zones towards north in Finland. Moreover, we explored possible size- and gender-dependent variation in pupal development duration. We divided wild-collected pupae in respect to their origin in two ways: (1) temperature zones (from south-west to colder north-east) and (2) invasion history (from early to late establishment). We reared pupae in the controlled laboratory conditions in identical temperature and light conditions. Pupal size decreased towards north and the smaller pupae developed faster. However, the results do not show differences in pupal size or developmental characteristics between the invasion zones. This supports the idea of rapid developmental plasticity of the deer ked and that not the invasion history but the current temperature regime determines the life history of the deer ked when invading towards a colder environment.

  20. A new embryonic pattern in parasitic wasps: divergence in early development may not be associated with lifestyle.

    PubMed

    Mancini, Donato; Garonna, Antonio P; Pedata, Paolo A

    2013-01-01

    Comparative embryogenesis of Encarsia formosa and Encarsia pergandiella (Hymenoptera Aphelinidae), two endoparasitoids of whiteflies (Hemiptera Aleyrodidae), revealed two strongly diverging developmental patterns. Indeed, the centrolecithal anhydropic egg of E. formosa developed through a superficial cleavage, as it occurs in Nasonia vitripennis, Apis mellifera, and Drosophila melanogaster. In contrast, the alecithal hydropic egg of E. pergandiella developed through holoblastic cleavage within a specialized extra-embryonic membrane (EEM). Since this developmental pattern evolved independently in several lineages of hymenopteran endoparasitoids, departures from the superficial cleavage mode have been argued to be strongly canalized in response to a shift from ecto- to endoparasitic lifestyle. Coexistence of both developmental patterns in two congeneric species suggests that alterations of early embryonic development may not be correlated with lifestyle. In addition, embryogenesis of E. pergandiella exhibited the following developmental novelties compared to other species possessing a hydropic egg: (i) polar body derivatives early acquired a cytoskeletal boundary prior to any other cellularization event; (ii) cellularization was asynchronous, starting with an early differentiation of a single apical blastomere at the end of the third cleavage; (iii) appearance of cytoskeletal boundaries of embryo blastomeres occurred between the third and fourth cleavages; (iv) the EEM originated through asynchronous participation of three separate lineages of cleavage nuclei, one of which associated with the polar body derivatives in a syncytium. Our results confirm a scenario of high plasticity in the early developmental strategies of hymenopteran endoparasitoids.

  1. Recent developments in the diagnosis of ectoparasite infections and disease through a better understanding of parasite biology and host responses.

    PubMed

    Wells, Beth; Burgess, Stewart T G; McNeilly, Tom N; Huntley, John F; Nisbet, Alasdair J

    2012-02-01

    Some conventional methods of diagnosis of ectoparasite infections can have low sensitivity and/or specificity. In addition, early infestations, sub-clinical and carrier hosts often go un-diagnosed, allowing infestations to spread. This review focuses on the important ectoparasites of human, livestock and companion animals for which improved diagnostic tools are either already in use, or in development. These advances in diagnostic technologies have resulted in improved treatment, control and preventative strategies for many ectoparasitic diseases. Immunodiagnostic methods have had a large impact, with the emergence of highly sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for sarcoptic and psoroptic mange, with further improved tests in development. In the present review, the advantages and limitations of such tests are discussed and the potential for future development explored. The increasing use of molecular tools, for example, PCR and other molecular methods, has improved our understanding of the epidemiology of ectoparasitic diseases, with practical consequences for community-based control programmes. Recently, the identification of specific signalling pathways during the host response to ectoparasites has led to the identification of disease biomarkers which, along with new technologies, such as multiplexed assays and microfluidic platforms, could lead to more cost-effective, rapid and accurate diagnosis of infectious diseases.

  2. Quantitative pixelwise myocardial perfusion maps from first-pass perfusion MRI.

    PubMed

    Weng, A M; Ritter, C O; Beer, M; Hahn, D; Köstler, H

    2014-07-01

    To calculate and evaluate absolute quantitative myocardial perfusion maps from rest first-pass perfusion MRI. 10 patients after revascularization of myocardial infarction underwent cardiac rest first-pass perfusion MRI. Additionally, perfusion examinations were performed in 12 healthy volunteers. Quantitative myocardial perfusion maps were calculated by using a deconvolution technique, and results were compared were the findings of a sector-based quantification. Maps were typically calculated within 3 min per slice. For the volunteers, myocardial blood flow values of the maps were 0.51 ± 0.16 ml g(-1) per minute, whereas sector-based evaluation delivered 0.52 ± 0.15 ml g(-1) per minute. A t-test revealed no statistical difference between the two sets of values. For the patients, all perfusion defects visually detected in the dynamic perfusion series could be correctly reproduced in the maps. Calculation of quantitative perfusion maps from myocardial perfusion MRI examinations is feasible. The absolute quantitative maps provide additional information on the transmurality of perfusion defects compared with the visual evaluation of the perfusion series and offer a convenient way to present perfusion MRI findings. Voxelwise analysis of myocardial perfusion helps clinicians to assess the degree of tissue damage, and the resulting maps are a good tool to present findings to patients.

  3. In vitro development of the fish parasite Hysterothylacium aduncum from the third larval stage recovered from a host to the third larval stage hatched from the egg.

    PubMed

    Adroher, F J; Malagón, D; Valero, A; Benítez, R

    2004-01-28

    Anisakids are parasitic nematodes of fish worldwide, producing economic and human health concerns. It is thus important to ascertain their in vitro life cycle in laboratory studies. Here we describe the in vitro development of third-stage larvae (L3) of Hysterothylacium aduncum isolated from blue whiting Micromesistius poutassou, to the hatching of L3 from eggs obtained from H. aduncum worms grown in GLIT medium (a modified mixture of Yaeger's LIT [Liver Infusion Tryptose] and Grace's media) at pH 4.0, 13 degrees C and with 5% CO2 in air. Under these conditions, L3 recovered from fish developed to mature adults (3.4 to 6.2 cm in length), with oviposition starting from Day 26 in culture. Fertilized eggs (mean size 64 x 52 microm) had a thick, rugose eggshell and were larger than unfertilized ones (mean size 49 x 42 microm), whose eggshells were thin and smooth. Eggs laid during the first and second week of oviposition, and maintained in 2.8% NaCl solution at 13 degrees C, developed to L3. Under these maintenance conditions, between 20.6 and 52.5% of the eggs laid during the first week developed into larvae. Motile larvae, enclosed in a sheath, hatched from between 2 and 11% of these eggs. The larvae started to hatch 23 d after deposition. These larvae were 144 to 215 microm in length, enclosed in a 237 to 305 microm-long sheath. This GLIT culture medium may help to study the biology of this and other anisakids.

  4. A novel extracorporeal kidney perfusion system: a concept model.

    PubMed

    Szajer, Michael; Shah, Gaurang; Kittur, Dilip; Searles, Bruce; Li, Lu; Bruch, David; Darling, Edward

    2004-01-01

    The number of patients awaiting kidney transplantation has more than doubled in the past decade while the number of available donor organs has seen only a modest increase, leading to a critical shortage of organs. In response to this extreme shortage, the criteria for accepting organs have been modified to include marginal donors such as non-heart beating donors (NHBD). In these kidneys, determining viability is important for success of transplantation. Therefore, a study was undertaken to develop a system that would allow the extracorporeal assessment of function and compatibility of the donor organ before the patient is exposed to the risks associated with surgery. Following bilateral nephrectomy, the kidneys of 10 pigs (approximately 30 kg) were connected to a commercially available hypothermic pulsatile kidney perfusion apparatus. This system was modified to allow for normothermic pulsatile renal perfusion using the potential recipient's blood, via vascular access. These kidneys were perfused with the animal's blood for a minimum of two hours while various parameters were monitored. Perfusion pressures were kept between 60 and 90 mmHg, which correlated to flows between 70 and 150 mL/min. A decrease in perfusion pressure with a concomitant rise in flow over the two-hour period served as a good predictor of a viable and compatible graft. The modified kidney preservation system allows the normothermic, pulsatile extracorporeal perfusion of donor kidneys with the ability to monitor resistance to flow and urine production. This model also allows observation of the kidney for signs of hyperacute rejection. Further research needs to be conducted in order to determine if the system represents a methodology to increase the pool of available donor organs.

  5. Positron emission tomography to assess hypoxia and perfusion in lung cancer

    PubMed Central

    Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM

    2014-01-01

    In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221

  6. PulseCam: high-resolution blood perfusion imaging using a camera and a pulse oximeter.

    PubMed

    Kumar, Mayank; Suliburk, James; Veeraraghavan, Ashok; Sabharwal, Ashutosh

    2016-08-01

    Measuring blood perfusion is important in medical care as an indicator of injury and disease. However, currently available devices to measure blood perfusion like laser Doppler flowmetry are bulky, expensive, and cumbersome to use. An alternative low-cost and portable camera-based blood perfusion measurement system has recently been proposed, but such camera-only system produces noisy low-resolution blood perfusion maps. In this paper, we propose a new multi-sensor modality, named PulseCam, for measuring blood perfusion by combining a traditional pulse oximeter with a video camera in a unique way to provide low noise and high-resolution blood perfusion maps. Our proposed multi-sensor modality improves per pixel signal to noise ratio of measured perfusion map by up to 3 dB and improves the spatial resolution by 2 - 3 times compared to best known camera-only methods. Blood perfusion measured in the palm using our PulseCam setup during a post-occlusive reactive hyperemia (PORH) test replicates standard PORH response curve measured using laser Doppler flowmetry device but with much lower cost and a portable setup making it suitable for further development as a clinical device.

  7. Review: comparison of PET rubidium-82 with conventional SPECT myocardial perfusion imaging

    PubMed Central

    Ghotbi, Adam A; Kjær, Andreas; Hasbak, Philip

    2014-01-01

    Nuclear cardiology has for many years been focused on gamma camera technology. With ever improving cameras and software applications, this modality has developed into an important assessment tool for ischaemic heart disease. However, the development of new perfusion tracers has been scarce. While cardiac positron emission tomography (PET) so far largely has been limited to centres with on-site cyclotron, recent developments with generator produced perfusion tracers such as rubidium-82, as well as an increasing number of PET scanners installed, may enable a larger patient flow that may supersede that of gamma camera myocardial perfusion imaging. PMID:24028171

  8. Development of 12 novel polymorphic microsatellite markers using a next generation sequencing approach for Spiculopteragia spiculoptera, a nematode parasite of deer.

    PubMed

    Patrelle, Cécile; Jouet, Damien; Lehrter, Véronique; Ferté, Hubert

    2014-09-01

    Twelve novel polymorphic microsatellite markers were produced and characterized for Spiculopteragia spiculoptera (Nematoda, Trichostrongyloidae) a common parasite of abomasum of Roe and Red deer, using next generation sequencing approach, and two multiplexes PCR were developed with these markers. Polymorphism of each locus was tested in 40 individuals of this species from diverse wild populations of cervids, and was tested for crossed-amplification on four other species of nematodes, close to S. spiculoptera among the Trichostrongyloidea: 20 Spiculopteragia houdemeri, 34 Ostertagia leptospicularis, 16 Ashworthius sidemi, and 25 Trichostrongylus spp. Our new microsatellite markers seem to be specific to Spiculopteragia spiculoptera since no amplifications were obtained for the four other species. The number of alleles per locus ranged from 2 to 12, the average observed and expected heterozygosity per locus ranged from 0.025 to 0.641 and from 0.049 to 0.664, respectively. Four of the 12 microsatellite loci showed significant deviations from Hardy-Weinberg equilibrium (which two slightly significant). One locus pair showed significant linkage disequilibrium (Sspi4 vs. Sspi8). Neither evidence of scoring error due to stuttering nor evidence of large allele dropout was found at all of the 12 loci, but evidence of null alleles was indicated at three loci because of general excess of homozygotes for most allele size classes. These polymorphic loci will be useful markers to study population genetics structure of Spiculopteragia spiculoptera in order to understand transfer and to explain the relationships between deer populations.

  9. Sporogonic Cycles Calculated Using Degree-Days, as a Basis for Comparison of Malaria Parasite Development in Different Eco-Epidemiological Settings in India.

    PubMed

    Singh, Poonam; Dhiman, Ramesh C

    2016-01-01

    In India, malaria transmission is prevalent across diverse geologies and ecologies. Temperature is one of the key determinants of malarial transmission, causing low endemicity in some areas than in others. Using a degree-day model, we estimated the maximum and minimum possible number of days needed to complete a malarial sporogonic cycle (SC), in addition to the possible number of SCs for Plasmodium vivax and Plasmodium falciparum under two different ecological settings with either low or high endemicity for malaria at different elevations. In Raikhalkhatta (in the Himalayan foothills) SCs were modeled as not occurring from November to February, whereas in Gandhonia village (forested hills), all but only one month were suitable for malarial SCs. A minimum of 6 days and maximum of 46 days were required for completion of one SC. Forested hilly areas were more suitable for malaria parasite development in terms of SCs (25 versus 21 for P. falciparum and 32 versus 27 for P. vivax). Degree-days also provided a climatic explanation for the current transmission of malaria at different elevations. The calculation of degree-days and possible SC has applications in the regional analysis of transmission dynamics and management of malaria in view of climate change.

  10. Examination of the relationship between host worm community structure on transmission of the parasite, Myxobolus cerebralis by developing taxon-specific probes for multiplex qPCR to identify worm taxa in stream communities

    NASA Astrophysics Data System (ADS)

    Fytilis, N.; Lamb, R.; Kerans, B.; Stevens, L.; Rizzo, D. M.

    2011-12-01

    Fish diseases are often caused by waterborne parasites, making them ideal systems for modeling the non-linear relationships between disease dynamics, stream dwelling oligochaete communities and geochemical features. Myxobolus cerebralis, the causative agent of whirling disease in salmonid fishes, has been a major contributor to the loss of wild rainbow trout populations in numerous streams within the Intermountain West. The parasite alternates between an invertebrate and vertebrate host, being transmitted between the sediment feeding worm Tubifex tubifex (T.tubifex) and salmonid fishes. Worm community biodiversity and abundance are influenced by biogeochemical features and have been linked to disease severity in fish. The worm (T.tubifex) lives in communities with 3-4 other types of worms in stream sediments. Unfortunately, taxonomic identification of oligochaetes is largely dependent on morphological characteristics of sexually mature adults. We have collected and identified ~700 worms from eight sites using molecular genetic probes and a taxonomic key. Additionally, ~1700 worms were identified using only molecular genetic probes. To facilitate distinguishing among tubificids, we developed two multiplex molecular genetic probe-based quantitative polymerase reaction (qPCR) assays to assess tubificid communities in the study area. Similar qPCR techniques specific for M.cerebralis used to determine if individual worms were infected with the parasite. We show how simple Bayesian analysis of the qPCR data can predict the worm community structure and reveal relationships between biodiversity of host communities and host-parasite dynamics. To our knowledge, this is the first study that combines molecular data of both the host and the parasite to examine the effects of host community structure on the transmission of a parasite. Our work can be extended to examine the links between worm community structure and biogeochemical features using molecular genetics and Bayesian

  11. [Parasitism and ecological parasitology].

    PubMed

    Balashov, Iu S

    2011-01-01

    Parasitism as one of the life modes is a general biological phenomenon and is a characteristic of all viruses, many taxa of bacteria, fungi, protists, metaphytes, and metazoans. Zooparasitology is focused on studies of parasitic animals, particularly, on their taxonomy, anatomy, life cycles, host-parasite relations, biocoenotic connections, and evolution. Ecological parasitology is a component of ecology, as the scientific study of the relation of living organisms with each other and their surroundings. In the present paper, critical analysis of the problems, main postulates, and terminology of the modern ecological parasitology is given.

  12. Bird brood parasitism.

    PubMed

    Stevens, Martin

    2013-10-21

    For many animals, the effort to rear their young is considerable. In birds, this often includes building nests, incubating eggs, feeding the chicks, and protecting them from predators. Perhaps for this reason, about 1% of birds (around 100 species) save themselves the effort and cheat instead. They are obligate brood parasites, laying their eggs in the nests of other species and leaving the hosts or foster parents to rear the foreign chicks for them. Some birds also cheat on individuals of the same species (intraspecific brood parasitism). Intraspecific brood parasitism has been reported in around 200 species, but is likely to be higher, as it can often only be detected by genetic analyses.

  13. Parasitism and phenotypic change in colonial hosts.

    PubMed

    Hartikainen, Hanna; Fontes, Inês; Okamura, Beth

    2013-09-01

    Changes in host phenotype are often attributed to manipulation that enables parasites to complete trophic transmission cycles. We characterized changes in host phenotype in a colonial host–endoparasite system that lacks trophic transmission (the freshwater bryozoan Fredericella sultana and myxozoan parasite Tetracapsuloides bryosalmonae). We show that parasitism exerts opposing phenotypic effects at the colony and module levels. Thus, overt infection (the development of infectious spores in the host body cavity) was linked to a reduction in colony size and growth rate, while colony modules exhibited a form of gigantism. Larger modules may support larger parasite sacs and increase metabolite availability to the parasite. Host metabolic rates were lower in overtly infected relative to uninfected hosts that were not investing in propagule production. This suggests a role for direct resource competition and active parasite manipulation (castration) in driving the expression of the infected phenotype. The malformed offspring (statoblasts) of infected colonies had greatly reduced hatching success. Coupled with the severe reduction in statoblast production this suggests that vertical transmission is rare in overtly infected modules. We show that although the parasite can occasionally infect statoblasts during overt infections, no infections were detected in the surviving mature offspring, suggesting that during overt infections, horizontal transmission incurs a trade-off with vertical transmission.

  14. Mechanisms of cellular invasion by intracellular parasites.

    PubMed

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  15. Evolution of plant parasitism among nematodes.

    PubMed

    Baldwin, J G; Nadler, S A; Adams, B J

    2004-01-01

    Despite extraordinary diversity of free-living species, a comparatively small fraction of nematodes are parasites of plants. These parasites represent at least three disparate clades in the nematode tree of life, as inferred from rRNA sequences. Plant parasites share functional similarities regarding feeding, but many similarities in feeding structures result from convergent evolution and have fundamentally different developmental origins. Although Tylenchida rRNA phylogenies are not fully resolved, they strongly support convergent evolution of sedentary endoparasitism and plant nurse cells in cyst and root-knot nematodes. This result has critical implications for using model systems and genomics to identify and characterize parasitism genes for representatives of this clade. Phylogenetic studies reveal that plant parasites have rich and complex evolutionary histories that involve multiple transitions to plant parasitism and the possible use of genes obtained by horizontal transfer from prokaryotes. Developing a fuller understanding of plant parasitism will require integrating more comprehensive and resolved phylogenies with appropriate choices of model organisms and comparative evolutionary methods.

  16. Regulation of Gene Expression in Protozoa Parasites

    PubMed Central

    Gomez, Consuelo; Esther Ramirez, M.; Calixto-Galvez, Mercedes; Medel, Olivia; Rodríguez, Mario A.

    2010-01-01

    Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis. PMID:20204171

  17. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  18. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Postcolonial Ecologies of Parasite and Host: Making Parasitism Cosmopolitan.

    PubMed

    Anderson, Warwick

    2016-04-01

    The interest of F. Macfarlane Burnet in host-parasite interactions grew through the 1920s and 1930s, culminating in his book, Biological Aspects of Infectious Disease (1940), often regarded as the founding text of disease ecology. Our knowledge of the influences on Burnet's ecological thinking is still incomplete. Burnet later attributed much of his conceptual development to his reading of British theoretical biology, especially the work of Julian Huxley and Charles Elton, and regretted he did not study Theobald Smith's Parasitism and Disease (1934) until after he had formulated his ideas. Scholars also have adduced Burnet's fascination with natural history and the clinical and public health demands on his research effort, among other influences. I want to consider here additional contributions to Burnet's ecological thinking, focusing on his intellectual milieu, placing his research in a settler society with exceptional expertise in environmental studies and pest management. In part, an ''ecological turn'' in Australian science in the 1930s, derived to a degree from British colonial scientific investments, shaped Burnet's conceptual development. This raises the question of whether we might characterize, in postcolonial fashion, disease ecology, and other studies of parasitism, as successful settler colonial or dominion science.

  20. A study on cerebral hemodynamic analysis of moyamoya disease by using perfusion MRI

    NASA Astrophysics Data System (ADS)

    Dong, Kyung-Rae; Goo, Eun-Hoe; Lee, Jae-Seung; Chung, Woon-Kwan

    2013-10-01

    This study examined the clinical applications of perfusion magnetic resonance imaging (MRI) in patients with moyamoya disease (MMD). Twenty-two patients with moyamoya disease (9 men and 13 women) with a mean age of 9.3 years (range: 4-22 years) were enrolled in this study. Perfusion MRI was performed by scanning the patients7.5 cm upward from the base of the cerebellum before their being process for post-treatment. The scan led to the acquisition of the following four map images: the cerebral blood volume (CBV), the cerebral blood flow (CBF), the mean transit time (MTT) for the contrast medium, and the time to peak (TTP) for the contrast medium. The lesions were assessed using the CBV, the CBF, the MTT and the TTP maps of perfusion MRI; the MTT and the TTP were measured in the lesion areas, as well as in the normal and the symmetric areas. Perfusion defects were recognizable in all four perfusion MRI maps, and the MTT and the TTP showed a conspicuous delay in the parts where perfusion defects were recognized. The MTT and the TTP images of perfusion MRI reflected a significant correlation between the degrees of stenosis and occlusion in the posterior cerebral artery (PCA), as well as the development of collateral vessels. The four perfusion MRI maps could be used to predict the degrees of stenosis and occlusion in the posterior circulation, as well as the development of the collateral vessels, which enabled a hemodynamic evaluation of the parts with perfusion defects. Overall, perfusion MRI is useful for the diagnosis and the treatment of moyamoya disease and can be applied to clinical practice.

  1. Whole body perfusion for hybrid aortic arch repair: evolution of selective regional perfusion with a modified extracorporeal circuit.

    PubMed

    Fernandes, Philip; Walsh, Graham; Walsh, Stephanie; O'Neil, Michael; Gelinas, Jill; Chu, Michael W A

    2017-04-01

    Patients undergoing hybrid aortic arch reconstruction require careful protection of vital organs. We believe that whole body perfusion with tailored dual circuitry may help to achieve optimal patient outcomes. Our circuit has evolved from a secondary circuit utilizing a cardioplegia delivery device for lower body perfusion to a dual-oxygenator circuit. This allows individually controlled regional perfusion with ease of switching from secondary to primary circuit for total body flow. The re-design allows for separate flow and temperature regulation with two oxygenators in parallel. All patients underwent a single-stage operation for simultaneous treatment of arch and descending aortic pathology via a sternotomy, using a hybrid frozen elephant trunk technique. We report six consecutive patients undergoing hybrid arch and frozen elephant trunk reconstruction using a dual-oxygenator circuit. Five patients underwent elective surgery and one was emergent. One patient had an acute dissection while three underwent concomitant procedures, including a Ross procedure and two valve-sparing root reconstructions. Three cases were redo sternotomies. The mean pump time was 358 ± 131 min, the aortic cross clamp time 243 ± 135 min, the cardioplegia volume of 33,208 ml ± 16,173, cerebral ischemia 0 min, lower body ischemia 76 ± 34 min and the average lower body perfusion time was 142 min. Two patients did not require any donor blood products. The median intensive care unit (ICU) and hospital lengths of stay (LOS) were two days and 10 days, respectively. The average peak serum lactate on CPB was 7.47 mmol/L and, at admission to the ICU, it was 3.37 mmol/L. Renal and respiratory failure developed in the salvage acute type A dissection patient. No other complications occurred in this series. Whole body perfusion as delivered through individually controlled dual-oxygenator circuitry allows maximum flexibility for hybrid aortic arch reconstruction. A modified circuit perfusion

  2. Localized Spatio-Temporal Constraints for Accelerated CMR Perfusion

    PubMed Central

    Akçakaya, Mehmet; Basha, Tamer A.; Pflugi, Silvio; Foppa, Murilo; Kissinger, Kraig V.; Hauser, Thomas H.; Nezafat, Reza

    2013-01-01

    Purpose To develop and evaluate an image reconstruction technique for cardiac MRI (CMR)perfusion that utilizes localized spatio-temporal constraints. Methods CMR perfusion plays an important role in detecting myocardial ischemia in patients with coronary artery disease. Breath-hold k-t based image acceleration techniques are typically used in CMR perfusion for superior spatial/temporal resolution, and improved coverage. In this study, we propose a novel compressed sensing based image reconstruction technique for CMR perfusion, with applicability to free-breathing examinations. This technique uses local spatio-temporal constraints by regularizing image patches across a small number of dynamics. The technique is compared to conventional dynamic-by-dynamic reconstruction, and sparsity regularization using a temporal principal-component (pc) basis, as well as zerofilled data in multi-slice 2D and 3D CMR perfusion. Qualitative image scores are used (1=poor, 4=excellent) to evaluate the technique in 3D perfusion in 10 patients and 5 healthy subjects. On 4 healthy subjects, the proposed technique was also compared to a breath-hold multi-slice 2D acquisition with parallel imaging in terms of signal intensity curves. Results The proposed technique results in images that are superior in terms of spatial and temporal blurring compared to the other techniques, even in free-breathing datasets. The image scores indicate a significant improvement compared to other techniques in 3D perfusion (2.8±0.5 vs. 2.3±0.5 for x-pc regularization, 1.7±0.5 for dynamic-by-dynamic, 1.1±0.2 for zerofilled). Signal intensity curves indicate similar dynamics of uptake between the proposed method with a 3D acquisition and the breath-hold multi-slice 2D acquisition with parallel imaging. Conclusion The proposed reconstruction utilizes sparsity regularization based on localized information in both spatial and temporal domains for highly-accelerated CMR perfusion with potential utility in free

  3. Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance

    PubMed Central

    Suwanarusk, Rossarin; Russell, Bruce; Ong, Alice; Sriprawat, Kanlaya; Chu, Cindy S.; PyaePhyo, Aung; Malleret, Benoit; Nosten, François; Renia, Laurent

    2015-01-01

    Objectives Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai–Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. Methods To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. Results P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7–4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6–2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. Conclusions Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria. PMID:25150147

  4. Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance.

    PubMed

    Suwanarusk, Rossarin; Russell, Bruce; Ong, Alice; Sriprawat, Kanlaya; Chu, Cindy S; PyaePhyo, Aung; Malleret, Benoit; Nosten, François; Renia, Laurent

    2015-01-01

    Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

    PubMed Central

    You, Hong; Gobert, Geoffrey N.; Cai, Pengfei; Mou, Rong; Nawaratna, Sujeevi; Fang, Guofu; Villinger, Francois; McManus, Donald P.

    2015-01-01

    To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines. PMID:25961574

  6. Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential.

    PubMed

    You, Hong; Gobert, Geoffrey N; Cai, Pengfei; Mou, Rong; Nawaratna, Sujeevi; Fang, Guofu; Villinger, Francois; McManus, Donald P

    2015-05-01

    To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines.

  7. Effects of combined diethylcarbamazine and albendazole treatment of bancroftian filariasis on parasite uptake and development in Culex pipiens L.

    PubMed

    Farid, Hoda A; Hammad, Ragaa E; Hassan, Marah M; Ramzy, Reda M R; El Setouhy, Maged; Weil, Gary J

    2005-07-01

    We studied effects of combined diethylcarbamazine (DEC) and albendazole (ALB) treatment on Wuchereria bancrofti microfilaria (MF) uptake and development of infective larvae (L3) in Culex pipiens. Consenting Egyptian adults with microfilaremia (MF > 300/mL) were treated with one or seven daily doses of DEC/ALB. Laboratory-reared mosquitoes were fed on subjects before and after treatment. MF uptake and infectivity (assessed by mosquito dissection) were reduced by 89.6% and 82.9%, respectively, 12 months after single-dose treatment and by 96.2% and 99.7%, respectively, after multi-dose treatment. The L3:mosquito ratio decreased by 88% to 0.082 after single-dose treatment and by 99.8% to 0.001 after multi-dose treatment. If high coverage rates can be achieved for several annual cycles, mass drug administration (MDA) with DEC/ALB has the potential to decrease transmission to unsustainable levels and eliminate filariasis in populations. Multi-dose MDA (especially in the first year) might interrupt transmission with fewer cycles than single-dose treatment.

  8. Parasitic Skin Infections for Primary Care Physicians.

    PubMed

    Dadabhoy, Irfan; Butts, Jessica F

    2015-12-01

    The 2 epidermal parasitic skin infections most commonly encountered by primary care physicians in developed countries are scabies and pediculosis. Pediculosis can be further subdivided into pediculosis capitis, corporis, and pubis. This article presents a summary of information and a review of the literature on clinical findings, diagnosis, and treatment of these commonly encountered parasitic skin infestations. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Development and validation of PCR-based assays for diagnosis of American cutaneous leishmaniasis and identification of the parasite species.

    PubMed

    Graça, Grazielle Cardoso da; Volpini, Angela Cristina; Romero, Gustavo Adolfo Sierra; Oliveira Neto, Manoel Paes de; Hueb, Marcia; Porrozzi, Renato; Boité, Mariana Côrtes; Cupolillo, Elisa

    2012-08-01

    In this study, PCR assays targeting different Leishmania heat-shock protein 70 gene (hsp70) regions, producing fragments ranging in size from 230-390 bp were developed and evaluated to determine their potential as a tool for the specific molecular diagnosis of cutaneous leishmaniasis (CL). A total of 70 Leishmania strains were analysed, including seven reference strains (RS) and 63 previously typed strains. Analysis of the RS indicated a specific region of 234 bp in the hsp70 gene as a valid target that was highly sensitive for detection of Leishmania species DNA with capacity of distinguishing all analyzed species, after polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). This PCR assay was compared with other PCR targets used for the molecular diagnosis of leishmaniasis: hsp70 (1400-bp region), internal transcribed spacer (ITS)1 and glucose-6-phosphate dehydrogenase (G6pd). A good agreement among the methods was observed concerning the Leishmania species identification. Moreover, to evaluate the potential for molecular diagnosis, we compared the PCR targets hsp70-234 bp, ITS1, G6pd and mkDNA using a panel of 99 DNA samples from tissue fragments collected from patients with confirmed CL. Both PCR-hsp70-234 bp and PCR-ITS1 detected Leishmania DNA in more than 70% of the samples. However, using hsp70-234 bp PCR-RFLP, identification of all of the Leishmania species associated with CL in Brazil can be achieved employing a simpler and cheaper electrophoresis protocol.

  10. Metabolomics and protozoan parasites.

    PubMed

    Paget, Timothy; Haroune, Nicolas; Bagchi, Sushmita; Jarroll, Edward

    2013-06-01

    In this review, we examine the state-of-the-art technologies (gas and liquid chromatography, mass spectroscopy and nuclear magnetic resonance, etc.) in the well-established area of metabolomics especially as they relate to protozoan parasites.

  11. Children and Parasitic Diseases

    MedlinePlus

    ... conditioned room, and wear protective clothing. Soil-transmitted helminth (STH) diseases ("helminth" means parasitic worm) are of major importance in ... later in life. It is caused by a helminth that spends part of its life cycle in ...

  12. Cytoskeleton of Apicomplexan Parasites

    PubMed Central

    Morrissette, Naomi S.; Sibley, L. David

    2002-01-01

    The Apicomplexa are a phylum of diverse obligate intracellular parasites including Plasmodium spp., the cause of malaria; Toxoplasma gondii and Cryptosporidium parvum, opportunistic pathogens of immunocompromised individuals; and Eimeria spp. and Theileria spp., parasites of considerable agricultural importance. These protozoan parasites share distinctive morphological features, cytoskeletal organization, and modes of replication, motility, and invasion. This review summarizes our current understanding of the cytoskeletal elements, the properties of cytoskeletal proteins, and the role of the cytoskeleton in polarity, motility, invasion, and replication. We discuss the unusual properties of actin and myosin in the Apicomplexa, the highly stereotyped microtubule populations in apicomplexans, and a network of recently discovered novel intermediate filament-like elements in these parasites. PMID:11875126

  13. Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir A; Yost, Michael J; Visconti, Richard; Twal, Waleed; Trusk, Thomas; Wen, Xuejun; Ozolanta, Iveta; Kadishs, Arnolds; Prestwich, Glenn D; Terracio, Louis; Markwald, Roger R

    2006-01-01

    Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current

  14. Monitoring perfusion changes in laser-treated tumors using laser doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Deans, Abby; Hess, Linda; Koss, Michael; Liu, Hong; Chen, Wei R.

    2006-02-01

    Laser Doppler perfusion monitors are effect tools in understanding blood flow in many different types of biological studies. Because the low-intensity lasers used in Doppler perfusion measurements must interact with moving blood cells, the depth of probe-able tissue is limited to the volume of tissue within the hemisphere of radius ~1mm from the probe tip. In addition, heterogeneities in surface perfusion make precise probe placement very important if one is comparing successive measurements. Consequently, useful tissue perfusion measurements have been difficult to obtain, especially in deep tissues. In this study, a new method was developed for monitoring deep-tissue blood perfusion directionally with the Laserflo laser Doppler perfusion probe. The probe was inserted just under the skin superficially to a rat prostatic tumor through the shaft of a 16-gauge needle, which was modified to allow the probe to be exposed without extending beyond the beveled needle tip. Perfusion measurements of the tumor surface or the skin were made by rotating the bevel to face either inside or outside. Using this technique, tumor tissue can be differentiated from either skin or muscle. To study the responses of tumor to light stimulation, an 805nm biomedical treatment laser was used to irradiate the tumor. The perfusion of the tumor surface was shown to decrease slightly with short treatment laser applications (1W for 30 seconds or 1 minute). After a longer treatment session (5 minutes), the perfusion of the tumor tissue increased significantly. However, with an even longer (10 minutes) treatment, the perfusion of the tumor surface was shown to decrease once again. This trend indicates that before laser heating becomes significant, the perfusion decreases for as yet poorly understood reasons. When laser heating becomes significant, after the five-minute session, the perfusion increases dramatically, corresponding to the expected dilation of blood vessels during tissue heating. After

  15. Transfusion-transmitted parasitic infections

    PubMed Central

    Singh, Gagandeep; Sehgal, Rakesh

    2010-01-01

    The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas’ disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply. PMID:20859503

  16. Transfusion-transmitted parasitic infections.

    PubMed

    Singh, Gagandeep; Sehgal, Rakesh

    2010-07-01

    The transmission of parasitic organisms through transfusion is relatively rare. Of the major transfusion-transmitted diseases, malaria is a major cause of TTIP in tropical countries whereas babesiosis and Chagas' disease pose the greatest threat to donors in the USA In both cases, this is due to the increased number of potentially infected donors. There are no reliable serologic tests available to screen donors for any of these organisms and the focus for prevention remains on adherence to donor screening guidelines that address travel history and previous infection with the etiologic agent. One goal is the development of tests that are able to screen for and identify donors potentially infectious for parasitic infections without causing the deferral of a large number of non-infectious donors or significantly increasing costs. Ideally, methods to inactivate the infectious organism will provide an element of added safety to the blood supply.

  17. Parasites in marine food webs

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2013-01-01

    Most species interactions probably involve parasites. This review considers the extent to which marine ecologists should consider parasites to fully understand marine communities. Parasites are influential parts of food webs in estuaries, temperate reefs, and coral reefs, but their ecological importance is seldom recognized. Though difficult to observe, parasites can have substantial biomass, and they can be just as common as free-living consumers after controlling for body mass and trophic level. Parasites have direct impacts on the energetics of their hosts and some affect host behaviors, with ecosystem-level consequences. Although they cause disease, parasites are sensitive components of ecosystems. In particular, they suffer secondary extinctions due to biodiversity loss. Some parasites can also return to a system after habitat restoration. For these reasons, parasites can make good indicators of ecosystem integrity. Fishing can indirectly increase or decrease parasite populations and the effects of climate change on parasites are likely to be equally as complex.

  18. The Pratylenchus penetrans Transcriptome as a Source for the Development of Alternative Control Strategies: Mining for Putative Genes Involved in Parasitism and Evaluation of in planta RNAi

    PubMed Central

    Vieira, Paulo; Eves-van den Akker, Sebastian; Verma, Ruchi; Wantoch, Sarah; Eisenback, Jonathan D.; Kamo, Kathryn

    2015-01-01

    The root lesion nematode Pratylenchus penetrans is considered one of the most economically important species within the genus. Host range studies have shown that nearly 400 plant species can be parasitized by this species. To obtain insight into the transcriptome of this migratory plant-parasitic nematode, we used Illumina mRNA sequencing analysis of a mixed population, as well as nematode reads detected in infected soybean roots 3 and 7 days after nematode infection. Over 140 million paired end reads were obtained for this species, and de novo assembly resulted in a total of 23,715 transcripts. Homology searches showed significant hit matches to 58% of the total number of transcripts using different protein and EST databases. In general, the transcriptome of P. penetrans follows common features reported for other root lesion nematode species. We also explored the efficacy of RNAi, delivered from the host, as a strategy to control P. penetrans, by targeted knock-down of selected nematode genes. Different comparisons were performed to identify putative nematode genes with a role in parasitism, resulting in the identification of transcripts with similarities to other nematode parasitism genes. Focusing on the predicted nematode secreted proteins found in this transcriptome, we observed specific members to be up-regulated at the early time points of infection. In the present study, we observed an enrichment of predicted secreted proteins along the early time points of parasitism by this species, with a significant number being pioneer candidate genes. A representative set of genes examined using RT-PCR confirms their expression during the host infection. The expression patterns of the different candidate genes raise the possibility that they might be involved in critical steps of P. penetrans parasitism. This analysis sheds light on the transcriptional changes that accompany plant infection by P. penetrans, and will aid in identifying potential gene targets for

  19. The Pratylenchus penetrans Transcriptome as a Source for the Development of Alternative Control Strategies: Mining for Putative Genes Involved in Parasitism and Evaluation of in planta RNAi.

    PubMed

    Vieira, Paulo; Eves-van den Akker, Sebastian; Verma, Ruchi; Wantoch, Sarah; Eisenback, Jonathan D; Kamo, Kathryn

    2015-01-01

    The root lesion nematode Pratylenchus penetrans is considered one of the most economically important species within the genus. Host range studies have shown that nearly 400 plant species can be parasitized by this species. To obtain insight into the transcriptome of this migratory plant-parasitic nematode, we used Illumina mRNA sequencing analysis of a mixed population, as well as nematode reads detected in infected soybean roots 3 and 7 days after nematode infection. Over 140 million paired end reads were obtained for this species, and de novo assembly resulted in a total of 23,715 transcripts. Homology searches showed significant hit matches to 58% of the total number of transcripts using different protein and EST databases. In general, the transcriptome of P. penetrans follows common features reported for other root lesion nematode species. We also explored the efficacy of RNAi, delivered from the host, as a strategy to control P. penetrans, by targeted knock-down of selected nematode genes. Different comparisons were performed to identify putative nematode genes with a role in parasitism, resulting in the identification of transcripts with similarities to other nematode parasitism genes. Focusing on the predicted nematode secreted proteins found in this transcriptome, we observed specific members to be up-regulated at the early time points of infection. In the present study, we observed an enrichment of predicted secreted proteins along the early time points of parasitism by this species, with a significant number being pioneer candidate genes. A representative set of genes examined using RT-PCR confirms their expression during the host infection. The expression patterns of the different candidate genes raise the possibility that they might be involved in critical steps of P. penetrans parasitism. This analysis sheds light on the transcriptional changes that accompany plant infection by P. penetrans, and will aid in identifying potential gene targets for

  20. Coevolution of parasite virulence and host mating strategies.

    PubMed

    Ashby, Ben; Boots, Michael

    2015-10-27

    Parasites are thought to play an important role in sexual selection and the evolution of mating strategies, which in turn are likely to be critical to the transmission and therefore the evolution of parasites. Despite this clear interdependence we have little understanding of parasite-mediated sexual selection in the context of reciprocal parasite evolution. Here we develop a general coevolutionary model between host mate preference and the virulence of a sexually transmitted parasite. We show when the characteristics of both the host and parasite lead to coevolutionarily stable strategies or runaway selection, and when coevolutionary cycling between high and low levels of host mate choosiness and virulence is possible. A prominent argument against parasites being involved in sexual selection is that they should evolve to become less virulent when transmission depends on host mating success. The present study, however, demonstrates that coevolution can maintain stable host mate choosiness and parasite virulence or indeed coevolutionary cycling of both traits. We predict that choosiness should vary inversely with parasite virulence and that both relatively long and short life spans select against choosy behavior in the host. The model also reveals that hosts can evolve different behavioral responses from the same initial conditions, which highlights difficulties in using comparative analysis to detect parasite-mediated sexual selection. Taken as a whole, our results emphasize the importance of viewing parasite-mediated sexual selection in the context of coevolution.