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Sample records for antimalarial sensitivity tests

  1. Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine

    OpenAIRE

    Islahudin, Farida; Khozoie, Combiz; Bates, Steven; Ting, Kang-Nee; Pleass, Richard J.; Avery, Simon V.

    2013-01-01

    Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model Saccharomyces cerevisiae. A genomewide yeast deletion strain collection was screened against CQ, revealing that bck1Δ and slt2Δ mutants of the cell wall integrity pathway are CQ hypersensitive. This phenotype was rescued with sorbi...

  2. In-vitro antimalarial activity of azithromycin against chloroquine sensitive and chloroquine resistant Plasmodium falciparum.

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    Biswas S

    2001-10-01

    Full Text Available BAKGROUND: The spread of drug resistance in Plasmodium falciparum has made the situation essential to look into new effective therapeutic agents like antibiotics. Azithromycin is a potential, chemotherapeutic agent which possesses antimalarial activity and favourable pharmacokinetic properties. It is an azalide microbiocide derived semi-synthetically from macrolide erythromycin. Like other antibiotics, the azalide azithromycin has ability to inhibit protein synthesis on 70S ribosomes. SETTINGS: Experimental study. SUBJECTS AND METHODS: The parasiticidal profile was studied in five chloroquine sensitive and five chloroquine resistant P. falciparum isolates obtained from various places of India. The antimalarial activity was evaluated in P. falciparum schizont maturation by short term culture for 24 hours and by exposing the parasites to the drug for 96 hours. Parasites synchronized at ring stage were put for culture with various concentrations of azithromycin dihydrate (0.01-40 micro/ml. RESULTS: At highest concentration (40 micro/ml, parasite growth was inhibited totally in all 10 isolates. Antimalarial activity at 96 hours was greater than at 24 hours in both chloroquine sensitive and resistant parasites, which may indicate that the inhibition of parasite growth may occur at clinically achievable concentration of the drug when parasites were exposed for several asexual cycles. CONCLUSION: Azithromycin shows a potential for eventual use alone or in combination in the treatment of chloroquine sensitive and resistant P. falciparum malaria.

  3. A new double-antibody sandwich ELISA targeting Plasmodium falciparum aldolase to evaluate anti-malarial drug sensitivity

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    Brun Reto

    2009-10-01

    Full Text Available Abstract Background The standard in vitro test to assess anti-malarial activity of chemical compounds is the [3H]hypoxanthine incorporation assay. It is a radioactivity-based method to measure DNA replication of Plasmodium in red blood cells. The method is highly reproducible, however, the handling of radioactive material is costly, hazardous and requires the availability of appropriate technology and trained staff. Several other ways to evaluate in vitro anti-malarial activity do exist, all with their own assets and limitations. Methods The newly developed double-antibody sandwich ELISA described here is based on the properties of a non-overlapping pair of monoclonal antibodies directed against Plasmodium falciparum aldolase. This glycolytic enzyme possesses some unique nucleotide sequences compared to the human isoenzymes and has been highly conserved through evolution. Out of twenty possibilities, the most sensitive antibody pair was selected and used to quantitatively detect parasite aldolase in infected blood lysates. Results A total of 34 compounds with anti-malarial activity were tested side-by-side by ELISA and the [3H]hypoxanthine incorporation assay. The novel ELISA provided IC50s closely paralleling those from the radioactivity-based assay (R = 0.99, p Conclusion The newly developed ELISA presents several advantages over the comparative method, the [3H]hypoxanthine incorporation assay. The assay is highly reproducible, less hazardous (involves no radioactivity and requires little and cheap technical equipment. Relatively unskilled personnel can conduct this user-friendly assay. All this makes it attractive to be employed in resource-poor laboratories.

  4. Antimalarial drug resistance: An overview

    OpenAIRE

    Antony, Hiasindh Ashmi; Parija, Subhash Chandra

    2016-01-01

    Malaria is a major public health burden throughout the world. Resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. Monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. It is important to understand the mechanism of the antimalarial drugs, a...

  5. Antimalarial Activity of Azadipeptide Nitriles

    OpenAIRE

    Löser, Reik; Gut, Jiri; Rosenthal, Philip J.; Frizler, Maxim; Gütschow, Michael; Andrews, Katherine T.

    2009-01-01

    Azadipeptide nitriles – novel cysteine protease inhibitors – display structure-dependent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant lines of cultured Plasmodium falciparum malaria parasites. Inhibition of parasite’s haemoglobin-degrading cysteine proteases was also investigated, revealing the azadipeptide nitriles as potent inhibitors of falcipain-2 and -3. A correlation between the cysteine protease-inhibiting activity and the antimalarial potential of...

  6. Reduction of anti-malarial consumption after rapid diagnostic tests implementation in Dar es Salaam: a before-after and cluster randomized controlled study

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    Swai Ndeniria

    2011-04-01

    Full Text Available Abstract Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (mRDTs on prescription of anti-malarials in urban Tanzania. Methods The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of mRDTs in all three hospitals and in six HF. Three HF without mRDTs were selected as matched controls. The use of routine mRDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1 anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2 anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after mRDT implementation. Results Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80 in intervention and 32% (9-54 in control HF. For quinine vials, the reduction was 63% (54-72 in intervention and an increase of 2.49 times (1.62-3.35 in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26. The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22% and control HF (60% (Risk ratio 0.30, 95%CI 0.14-0.70. Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic

  7. Antimalarial drug resistance: An overview.

    Science.gov (United States)

    Antony, Hiasindh Ashmi; Parija, Subhash Chandra

    2016-01-01

    Malaria is a major public health burden throughout the world. Resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. Monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. It is important to understand the mechanism of the antimalarial drugs, as it is one of the key factors in the emergence and spread of drug resistance. This review summarizes the commonly used antimalarial drugs, their mechanism of action and the genetic markers validated so far for the detection of drug-resistant parasites. PMID:26998432

  8. In vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine

    OpenAIRE

    Sahu, Rajnish; Walker, Larry A.; Tekwani, Babu L.

    2014-01-01

    Background Several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. Tigecycline, a semi-synthetic derivative of minocycline with a unique and novel mechanism of action, is the first clinically available drug in a new class of glycylcycline antibiotics. Methods Tigecycline was tested in vitro against chloroquine (CQ)-sensitive (D6) and resistant strains (W2) of Plasmodium falcip...

  9. Benefits of a new Metropolis-Hasting based algorithm, in non-linear regression for estimation of ex vivo antimalarial sensitivity in patients infected with two strains.

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    Bauer, Rebecca; Mentré, France; Kaddouri, Halima; Le Bras, Jacques; Le Nagard, Hervé

    2014-12-01

    Malaria is one of the world׳s most widespread parasitic diseases. The parasitic protozoans of the genus Plasmodium have developed resistance to several antimalarial drugs. Some patients are therefore infected by two or more strains with different levels of antimalarial drug sensitivity. We previously developed a model to estimate the drug concentration (IC50) that inhibits 50% of the growth of the parasite isolated from a patient infected with one strain. We propose here a new Two-Slopes model for patients infected by two strains. This model involves four parameters: the proportion of each strain and their IC50, and the sigmoidicity parameter. To estimate the parameters of this model, we have developed a new algorithm called PGBO (Population Genetics-Based Optimizer). It is based on the Metropolis-Hasting algorithm and is implemented in the statistical software R. We performed a simulation study and defined three evaluation criteria to evaluate its properties and compare it with three other algorithms (Gauss-Newton, Levenberg-Marquardt, and a simulated annealing). We also evaluated it using in vitro data and three ex vivo datasets from the French Malaria Reference Center. Our evaluation criteria in the simulation show that PGBO gives good estimates of the parameters even if the concentration design is poor. Moreover, our algorithm is less sensitive than Gauss-Newton algorithms to initial values. Although parameter estimation is good, interpretation of the results can be difficult if the proportion of the second strain is close to 0 or 1. For these reasons, this approach cannot yet be implemented routinely. PMID:25450214

  10. An analysis of sensitivity tests

    Energy Technology Data Exchange (ETDEWEB)

    Neyer, B.T.

    1992-03-06

    A new method of analyzing sensitivity tests is proposed. It uses the Likelihood Ratio Test to compute regions of arbitrary confidence. It can calculate confidence regions for the parameters of the distribution (e.g., the mean, {mu}, and the standard deviation, {sigma}) as well as various percentiles. Unlike presently used methods, such as those based on asymptotic analysis, it can analyze the results of all sensitivity tests, and it does not significantly underestimate the size of the confidence regions. The main disadvantage of this method is that it requires much more computation to calculate the confidence regions. However, these calculations can be easily and quickly performed on most computers.

  11. Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

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    Mariana Conceição Souza

    2015-06-01

    Full Text Available A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3 inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

  12. Anticancer properties of distinct antimalarial drug classes.

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    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  13. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

    OpenAIRE

    Timothy J. Hubin; Amoyaw, Prince N. -A.; Roewe, Kimberly D.; Simpson, Natalie C.; Maples, Randall D.; Carder Freeman, TaRynn N.; Amy N. Cain; Le, Justin G.; Stephen J Archibald; Khan, Shabana I.; Tekwani, Babu L.; Khan, M. O. Faruk

    2014-01-01

    Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal comple...

  14. On peroxide antimalarials

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    IGOR OPSENICA

    2007-12-01

    Full Text Available Several dicyclohexylidene tetraoxanes were prepared in order to gain a further insight into structure–activity relationship of this kind of antimalarials. The tetraoxanes 2–5, obtained as a cis/trans mixture, showed pronounced antimalarial activity against Plasmodium falciparum chloroquine susceptible D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand strains. They have better than or similar activity to the corresponding desmethyl dicyclohexylidene derivatives. Two chimeric endoperoxides with superior antimalarial activity to the natural product ascaridole were also synthesized.

  15. Development of a TaqMan Allelic Discrimination Assay for detection of Single Nucleotides Polymorphisms associated with anti-malarial drug resistance

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    Kamau Edwin

    2012-01-01

    Full Text Available Abstract Background Anti-malarial drug resistance poses a threat to current global efforts towards control and elimination of malaria. Several methods are used in monitoring anti-malarial drug resistance. Molecular markers such as single nucleotide polymorphism (SNP for example are increasingly being used to identify genetic mutations related to anti-malarial drug resistance. Several methods are currently being used in analysis of SNP associated with anti-malarial drug resistance and although each one of these methods has unique strengths and shortcoming, there is still need to improve and/or develop new methods that will close the gap found in the current methods. Methods TaqMan Allelic Discrimination assays for detection of SNPs associated with anti-malarial drug resistance were designed for analysis on Applied Biosystems PCR platform. These assays were designed by submitting SNP sequences associated with anti-malarial drug resistance to Applied Biosystems website. Eleven SNPs associated with resistance to anti-malarial drugs were selected and tested. The performance of each SNP assay was tested by creating plasmid DNAs carrying codons of interests and analysing them for analysis. To test the sensitivity and specificity of each SNP assay, 12 clinical samples were sequenced at codons of interest and used in the analysis. Plasmid DNAs were used to establish the Limit of Detection (LoD for each assay. Results Data from genetic profiles of the Plasmodium falciparum laboratory strains and sequence data from 12 clinical samples was used as the reference method with which the performance of the SNP assays were compared to. The sensitivity and specificity of each SNP assay was establish at 100%. LoD for each assay was established at 2 GE, equivalent to less than 1 parasite/μL. SNP assays performed well in detecting mixed infection and analysis of clinical samples. Conclusion TaqMan Allelic Discrimination assay provides a good alternative tool in

  16. In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

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    Eberlin Marcos N

    2011-05-01

    Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

  17. Tyrosine kinase inhibitors: New class of antimalarials on the horizon?

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    Pathak, Vrushali; Colah, Roshan; Ghosh, Kanjaksha

    2015-08-01

    Development of the antimalarial drug resistant strains has currently become a major public health challenge. There is an urgent need to develop new antimalarial drugs. Tyrosine kinase inhibitors (TKIs) are receiving increasing attention as anticancer therapy. It has revolutionarised the management of CML to say the least. TKIs are also increasingly being implicated in complicated but vital life cycle of malaria parasite. Hence we tested two commonly used but different classes of TKIs (imatinib and sorafenib) in-vitro for their antimalarial activity and possible synergistic activity with existing antimalarial drug. Antimalarial activity was tested with the help of modified WHO microtest technique in-vitro for five different Plasmodium falciparum laboratory strains (3D7, Dd2, 7G8, MRC2, PKL9). Imatinib and sorafenib showed a promising antimalarial activity with all the strains. These compounds caused dose dependent inhibition of parasite maturation. The isobologram analysis of the interactions of these TKIs with standard antimalarial drug, artesunate revealed distinct patterns of synergism, additivity and antagonism at different ratios. Imatinib showed worthwhile synergism with artesunate indicating imatinib and other tyrosine kinase inhibitors may have significant antimalarial activity and can be used in combination therapy. PMID:26142327

  18. Antimalarial natural products: a review

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    Faraz Mojab

    2012-03-01

    Results and Conclusion: There is an urgent need for the development of new treatments for malaria. Many countries have a vast precedence in the use of medicinal plants and the required knowledge spans many centuries. Although malaria is controlled in Iran, some researchers tend to study malaria and related subjects. In vitro biological tests for the detection of antimalarial activities in plant extracts are currently available. It is vital that the efficacy and safety of traditional medicines be validated and their active constituents be identified in order to establish reliable quality control measures.

  19. Surveillance of antimalarial drug resistance in China in the 1980s–1990s

    OpenAIRE

    Liu, De-Quan

    2014-01-01

    Since the successful preparation of the microplates and the medium for field application, the resistance degree and its geographical distribution of chloroquine-resistant Plasmodium falciparum, the fluctuation of the resistance degree of P. falciparum to chloroquine, and the sensitivity of the parasite to commonly used antimalarial drugs were investigated between 1980 and 2003 by the in vitro microtest and the in vivo four-week test recommended by the World Health Organization (WHO). The resu...

  20. Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads

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    Lucio H. Freitas-Junior

    2013-08-01

    Full Text Available Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria.

  1. In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids

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    Birgit Viira

    2016-06-01

    Full Text Available Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery.

  2. Parametric Sensitivity Tests- European PEM Fuel Cell Stack Test Procedures

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    As fuel cells are increasingly commercialized for various applications, harmonized and industry-relevant test procedures are necessary to benchmark tests and to ensure comparability of stack performance results from different parties. This paper reports the results of parametric sensitivity tests...

  3. Antimicrobial and antimalarial properties of medicinal plants used by the indigenous tribes of Andaman and Nicobar Islands, India.

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    Chander, M Punnam; Pillai, C R; Sunish, I P; Vijayachari, P

    2016-07-01

    In this study, methanol extracts of six medicinal plants (Alstonia macrophylla, Claoxylon indicum, Dillenia andamanica, Jasminum syringifolium, Miliusia andamanica and Pedilanthus tithymaloides) traditionally used by Nicobarese tribes of Andaman and Nicobar Islands were studied for antimicrobial and antimalarial activities as well as preliminary photochemical analysis. Plants were collected from Car Nicobar of Andaman and Nicobar Islands and the ethnobotanical data were gathered from traditional healers who inhabit the study area. The methanol extracts were obtained by cold percolation method and the antimicrobial activity was found using agar well diffusion method. Among the plants tested, J. syringifolium, D. andamanica, C. indicum were most active. The antimalarial activity was evaluated against Plasmodium falciparum chloroquine-sensitive MRC-2 isolate. The crude extract of M. andamanica showed excellent antimalarial activity followed by extracts of P. tithymaloides, J. syringifolium and D. andamanica. The chemical injury to erythrocytes was also carried out and it showed that, there were no morphological changes in erythrocytes by the methanol crude extracts. The in vitro antimicrobial and antimalarial activity might be due to the presence of alkaloids, flavonoids, triterpenes, sterols, tannins and saponins in the methanol extracts of tested plants. PMID:27174207

  4. In vitro antimalarial drug susceptibility in Thai border areas from 1998–2003

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    Mungthin Mathirut

    2005-08-01

    Full Text Available Abstract Background The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003,. Methods Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA] was determined by the isotopic microtest. Results Mefloquine (MQ sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002 of low level MQ resistance (p = 000001. Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN. Conclusion This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many

  5. Impact sensitivity test of liquid explosives

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    Tiutiaev, Andrei; Trebunskih, Valeri; Dolzhikov, Andrei; Zvereva, Irina

    2015-06-01

    The sensitivity of liquid explosive in the presence of gas bubbles increases many times as compared with the liquid without gas bubbles. If we consider that in the liquid as a result of convection, wave motion, shock, etc. gas bubbles are easily generated, the need to develop a method for determining sensitivity of liquid explosives to impact and a detailed study of the ignition explosives with bubbles is obvious. On a mathematical model of a single steam bubbles in the fluid theoretically considered the process of initiating explosive liquid systems to impact. For the experimental investigation, the well-known K-44 -II and the so-called appliance No. 1 were used. Instead of the metal cap in the standard method in this paper there was polyurethane foam cylindrical container with LHE, which is easily deforms by impact. A large number of tests with different liquid explosives were made. It was found that the test LHE to impact in appliance No. 1 with polyurethane foam to a large extent reflect the real mechanical sensitivity due to the small loss of impact energy on the deformation of the metal cap, as well as the best differentiation LHE sensitivity due to the higher resolution method .

  6. Antimalarial activity of some Colombian medicinal plants

    OpenAIRE

    Garavito, G. (G.); Rincon, J.; Arteaga, L.; Hata, Y; Bourdy, Geneviève; Gimenez, A.; Pinzon, R.; Deharo, Eric

    2006-01-01

    Antimalarial activity of 10 vegetal extracts (9 ethanolic extracts and 1 crude alkaloid extract), obtained from eight species traditionally used in Colombia to treat malaria symptoms, was evaluated in culture using Plasmodium falciparum chloroquine resistant (FcB2) strain and in vivo on rodent malaria Plasmodium berghei. The activity on ferriprotoporphyrin biomineralization inhibition test (FBIT) was also assessed. Against Plasmodium falciparum, eight extracts displayed good activity Abuta gr...

  7. Estimating the Impact of Means-tested Subsidies under Treatment Externalities with Application to Anti-Malarial Bednets

    DEFF Research Database (Denmark)

    Bhattacharya, Debopam; Dupas, Pascaline; Kanaya, Shin

    Regular use of effective health-products such as insecticide-treated mosquito nets (ITN) by a household benefits its neighbors by (a) reducing chances of infection and (b) raising awareness about product-effectiveness, thereby increasing product-use. Due to their potential social benefits and high...... its neighbors. Using experimental data from Kenya where subsidies were randomized, coupled with GPS-based location information, we show how to estimate aggregate ITN use resulting from means-tested subsidies in the presence of such spatial spillovers. Accounting for spillovers introduces infinite......-dimensional estimated regressors corresponding to continuously distributed location coordinates and makes the inference problem novel. We show that even if individual ITN use unambiguously increases with increasing incidence of subsidy in the neighborhood, ignoring spillovers may over- or under-predict overall ITN use...

  8. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Directory of Open Access Journals (Sweden)

    Jason P Wendler

    Full Text Available BACKGROUND: Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. METHODS AND PRINCIPAL FINDINGS: Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. CONCLUSIONS/SIGNIFICANCE: Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

  9. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

    Directory of Open Access Journals (Sweden)

    Swain Bijay K

    2009-02-01

    Full Text Available Abstract Background Herbal extracts of Andrographis paniculata (AP and Hedyotis corymbosa (HC are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20 and resistant (MRC-pf-303 strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50 of AP (7.2 μg/ml was found better than HC (10.8 μg/ml. Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC and their individual synergism with curcumin (AP+CUR, HC+CUR were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

  10. The interaction of x-rays and antimalarials

    International Nuclear Information System (INIS)

    Full text: The radiation sensitivity of malaria parasites has three potential clinical applications, namely i) to prevent the transmission of malaria by blood transfusion, ii) as adjunctive therapy when a radioactive isotope is complexed to a conventional antimalarial drug, and iii) to attenuate the pathogenicity of specific parasite stages as part of the development of a vaccine. In the first two applications, detailed information relating to parasite radiosensitivity and the interaction of ionising radiation with antimalarials is of vital importance because dosimetry must allow for the exposure of normal cells. Malaria parasite cultures (Plasmodium falciparum) were exposed to a logarithmic series of concentrations of antimalarial agents and irradiated using a Siemens Stabilipan orthovoltage radiotherapy unit. The irradiation was performed at room temperature and ambient oxygen concentration. Control samples were also irradiated. The DNA synthesis in each culture was measured 48 hours post irradiation by using a 3H-hypoxanthine incorporation assay. The antimalarials studied are: artesunate, quinine, retinol and chloroquine. The radiosensitivity of Plasmodium falciparum is not dependent on the strain of parasite with the dose required to inhibit 50% of DNA synthesis (ID50) equal to 24.7 ± 3.0 Gy. This applies equally for the drug resistant and drug sensitive strains studied. Because the measured radiosensitivity is dependent on the sera oxygen concentration, the reported value for the ID50 may not apply in hypoxic situations. The interaction of ionising radiation with the antimalarials shows synergy with retinol and choloquine, additivity with quinine and slight antagonism with artesunate. Radionuclide therapy may emerge as a novel treatment for malaria. If this does occur, then, although all strains appear to be equally radiosensitive, care must be taken when combining ionising radiation with existing antimalarials for the treatment of malaria. Copyright (2001

  11. Characterization of PfTrxR inhibitors using antimalarial assays and in silico techniques

    OpenAIRE

    Munigunti, Ranjith; Gathiaka, Symon; Acevedo, Orlando; Sahu, Rajnish; Tekwani, Babu; Calderón, Angela I.

    2013-01-01

    Background The compounds 1,4-napthoquinone (1,4-NQ), bis-(2,4-dinitrophenyl)sulfide (2,4-DNPS), 4-nitrobenzothiadiazole (4-NBT), 3-dimethylaminopropiophenone (3-DAP) and menadione (MD) were tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay and also for analysis of non-covalent interactions with P. falciparum thioredoxin reductase (PfTrxR) through in silico docking studies...

  12. New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

    Science.gov (United States)

    Soares, Roberta Reis; da Silva, José Marcio Fernandes; Carlos, Bianca Cecheto; da Fonseca, Camila Campos; de Souza, Laila Salomé Araújo; Lopes, Fernanda Valério; de Paula Dias, Rafael Mafra; Moreira, Paulo Otávio Lourenço; Abramo, Clarice; Viana, Gustavo Henrique Ribeiro; de Pila Varotti, Fernando; da Silva, Adilson David; Scopel, Kézia Katiani Gorza

    2015-06-01

    Malaria continues to be an important public health problem in the world. Nowadays, the widespread parasite resistance to many drugs used in antimalarial therapy has made the effective treatment of cases and control of the disease a constant challenge. Therefore, the discovery of new molecules with good antimalarial activity and tolerance to human use can be really important in the further treatment of the disease. In this study we have investigated the antiplasmodial activity of 10 synthetic compounds derived from quinoline, five of them combined to sulfonamide and five to the hydrazine or hydrazide group. The compounds were evaluated according to their cytotoxicity against HepG2 and HeLa cell lines, their antimalarial activity against CQ-sensitive and CQ-resistant Plasmodium falciparum strains and, finally, their schizonticide blood action in mice infected with Plasmodium berghei NK65. The compounds exhibited no cytotoxic action in HepG2 and HeLa cell lines when tested up to a concentration of 100 μg/mL. In addition, the hydrazine or hydrazide derivative compounds were less cytotoxic against cell lines and more active against CQ-sensitive and CQ-resistant P. falciparum strains, showing high SI (>1000 when SI was calculated using the CC50 from the 3D7 strain as reference). When tested in vivo, the hydrazine derivative 1f compound showed activity against the development of blood parasites similar to that observed with CQ, the reference drug. Interestingly, the 1f compound demonstrated the best LipE value (4.84) among all those tested in vivo. Considering the in vitro and in vivo activities of the compounds studied here and the LipE values, we believe the 1f compound to be the most promising molecule for further studies in antimalarial chemotherapy. PMID:25920564

  13. High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations.

    Science.gov (United States)

    Mott, Bryan T; Eastman, Richard T; Guha, Rajarshi; Sherlach, Katy S; Siriwardana, Amila; Shinn, Paul; McKnight, Crystal; Michael, Sam; Lacerda-Queiroz, Norinne; Patel, Paresma R; Khine, Pwint; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Fontaine, Shaun D; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A; Ferrer, Marc; Renslo, Adam R; Inglese, James; Yuan, Jing; Roepe, Paul D; Su, Xin-Zhuan; Thomas, Craig J

    2015-01-01

    Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy. PMID:26403635

  14. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

    OpenAIRE

    Swain Bijay K; Dash Aditya P; Mishra Kirti; Dey Nrisingha

    2009-01-01

    Abstract Background Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using diff...

  15. Detecting Counterfeit Antimalarial Tablets by Near-Infrared Spectroscopy

    Science.gov (United States)

    Counterfeit antimalarial drugs are found in many developing countries, but it is challenging to differentiate between genuine and fakes due to their increasing sophistication. Near-infrared spectroscopy (NIRS) is a powerful tool in pharmaceutical forensics, and we tested this technique for discrim...

  16. Highly sensitive silicon microreactor for catalyst testing

    DEFF Research Database (Denmark)

    Henriksen, Toke Riishøj; Olsen, Jakob Lind; Vesborg, Peter Christian Kjærgaard;

    2009-01-01

    A novel microfabricated chemical reactor for highly sensitive measurements of catalytic activity and surface kinetics is presented. The reactor is fabricated in a silicon chip and is intended for gas-phase reactions at pressures ranging from 0.1 to 5.0 bar. A high sensitivity is obtained by...... catalysts which can only be obtained in small quantities. Such measurements are of significant fundamental interest but are challenging because of the low surface areas involved. The relationship between the reaction zone gas flow and the pressure in the reaction zone is investigated experimentally. A...

  17. Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Daria Van Tyne

    2011-04-01

    Full Text Available The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (∼ 1 SNP/kb, and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS, searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.

  18. An in vitro human skin test for assessing sensitization potential.

    Science.gov (United States)

    Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

    2016-05-01

    Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. PMID:26251951

  19. In vitro antimalarial activity of novel semisynthetic nocathiacin I antibiotics.

    Science.gov (United States)

    Sharma, Indu; Sullivan, Margery; McCutchan, Thomas F

    2015-01-01

    Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in vitro growth inhibition assay was done using three laboratory strains of P. falciparum displaying various levels of chloroquine (CQ) susceptibility. Our results indicate that BMS461996 has potent antimalarial activity and inhibits parasite growth with mean 50% inhibitory concentrations (IC50s) of 51.55 nM for P. falciparum 3D7 (CQ susceptible), 85.67 nM for P. falciparum Dd2 (accelerated resistance to multiple drugs [ARMD]), and 99.44 nM for P. falciparum K1 (resistant to CQ, pyrimethamine, and sulfadoxine). Similar results at approximately 7-fold higher IC50s were obtained with BMS411886 than with BMS461996. We also tested the effect of BMS491996 on gametocytes; our results show that at a 20-fold excess of the mean IC50, gametocytes were deformed with a pyknotic nucleus and growth of stage I to IV gametocytes was arrested. This preliminary study shows a significant potential for nocathiacin analogues to be developed as antimalarial drug candidates and to warrant further investigation. PMID:25779576

  20. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya.

    Science.gov (United States)

    Koch, A; Tamez, P; Pezzuto, J; Soejarto, D

    2005-10-01

    Semi-structured interviews with three Maasai herbalists led to the identification and collection of 21 species of plants used to treat malaria. Extracts were evaluated using in vitro antimalarial and cytotoxicity assays. Of the species tested, over half were antiplasmodial (IC5020 microg/ml) against cultured KB cells. The results of this preliminary investigation support the traditional knowledge of Maasai herbalists and justify ethnomedical inquiry as a promising method, specifically, in antimalarial therapy, to yield leads for drug discovery. PMID:15878245

  1. Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake

    Directory of Open Access Journals (Sweden)

    Carmen E Contreras

    2004-03-01

    Full Text Available The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

  2. Comparison of the sensitivities of the Buehler test and the guinea pig maximization test for predictive testing of contact allergy

    DEFF Research Database (Denmark)

    Frankild, S; Vølund, A; Wahlberg, J E;

    2001-01-01

    dose-response model. To compare the sensitivity of the 2 test procedures the test conditions were kept identical and the following chemicals with a range of sensitization potentials were tested: chloraniline, chlorhexidine, eugenol, formaldehyde, mercaptobenzothiazole and neomycin sulphate....... Formaldehyde and neomycin sulphate were strong sensitizers in both tests. Mercaptobenzothiazole, eugenol and chloraniline were all strong sensitizers in the GPMT, eugenol and mercaptobenzothiazole were negative in the Buehler test and equivocal results were obtained with chloraniline. Chlorhexidine was...

  3. Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network.

    Science.gov (United States)

    Cui, Liwang; Mharakurwa, Sungano; Ndiaye, Daouda; Rathod, Pradipsinh K; Rosenthal, Philip J

    2015-09-01

    Antimalarial drugs are key tools for the control and elimination of malaria. Recent decreases in the global malaria burden are likely due, in part, to the deployment of artemisinin-based combination therapies. Therefore, the emergence and potential spread of artemisinin-resistant parasites in southeast Asia and changes in sensitivities to artemisinin partner drugs have raised concerns. In recognition of this urgent threat, the International Centers of Excellence for Malaria Research (ICEMRs) are closely monitoring antimalarial drug efficacy and studying the mechanisms underlying drug resistance. At multiple sentinel sites of the global ICEMR network, research activities include clinical studies to track the efficacies of antimalarial drugs, ex vivo/in vitro assays to measure drug susceptibilities of parasite isolates, and characterization of resistance-mediating parasite polymorphisms. Taken together, these efforts offer an increasingly comprehensive assessment of the efficacies of antimalarial therapies, and enable us to predict the emergence of drug resistance and to guide local antimalarial drug policies. Here we briefly review worldwide antimalarial drug resistance concerns, summarize research activities of the ICEMRs related to drug resistance, and assess the global impacts of the ICEMR programs. PMID:26259943

  4. Evaluating the Instructional Sensitivity of Four States' Student Achievement Tests

    Science.gov (United States)

    Polikoff, Morgan S.

    2016-01-01

    As state tests of student achievement are used for an increasingly wide array of high- and low-stakes purposes, evaluating their instructional sensitivity is essential. This article uses data from the Bill and Melinda Gates Foundation's Measures of Effective Project to examine the instructional sensitivity of 4 states' mathematics and English…

  5. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense

    Directory of Open Access Journals (Sweden)

    Khodakarim Nastaran

    2010-05-01

    Full Text Available Abstract Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain and CY27 (chloroquine-sensitive strain, using the parasite lactate dehydrogenase (pLDH assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain. Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy, Solanum surattense (Burm.f. and Prosopis juliflora (Sw. showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.

  6. Vendor Testing of Sensitive Compounds in Simulated Dry Sludge

    International Nuclear Information System (INIS)

    This assessment covers thermal screening, differential scanning calorimetry, and impact sensitivity testing on Mercury Fulminate, and mixtures of the fulminate in dry inorganic sludge, which is present in large quantities in a number of storage tanks at Westinghouse Savannah River

  7. Stressful events and psychological difficulties : Testing alternative candidates for sensitivity

    NARCIS (Netherlands)

    Laceulle, Odilia M.; O'Donnell, Kieran; Glover, Vivette; O'Connor, Thomas G.; Ormel, Johan; Van Aken, Marcel A G; Nederhof, Esther

    2014-01-01

    The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that

  8. Stressful events and psychological difficulties : testing alternative candidates for sensitivity

    NARCIS (Netherlands)

    Laceulle, Odilia M.; O'Donnell, Kieran; Glover, Vivette; O'Connor, Thomas G.; Ormel, Johan; van Aken, Marcel A. G.; Nederhof, Esther

    2014-01-01

    The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that

  9. Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Garavito G.

    2007-06-01

    Full Text Available Methylene blue (MB is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy.

  10. The Development of Moisture Sensitivity Test for Compacted Asphalt

    OpenAIRE

    M.K. Shamshuddin; M.E. Abdullah; Rhasbudin Shah, S.M.

    2011-01-01

    Moisture damage is one of the major issues in asphalt distress. It is due to the adhesive and cohesive failure of asphalt mixture and it will shorten pavement life. Moisture-sensitive mixtures need to be identified during the course of the mixture design process which fulfills the specified minimum standard. The laboratory testing procedures currently available for compacted Hot Mix Asphalt (HMA) to test the moisture sensitivity were primarily developed to determine the degree ...

  11. Non-animal test methods for predicting skin sensitization potentials.

    Science.gov (United States)

    Mehling, Annette; Eriksson, Tove; Eltze, Tobias; Kolle, Susanne; Ramirez, Tzutzuy; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2012-08-01

    Contact allergies are complex diseases, and it is estimated that 15-20 % of the general population suffers from contact allergy, with increasing prevalence. Evaluation of the sensitization potential of a substance is usually carried out in animal models. Nowadays, there is much interest in reducing and ultimately replacing current animal tests. Furthermore, as of 2013, the EU has posed a ban on animal testing of cosmetic ingredients that includes skin sensitization. Therefore, predictive and robust in vitro tests are urgently needed. In order to establish alternatives to animal testing, the in vitro tests must mimic the very complex interactions between the sensitizing chemical and the different parts of the immune system. This review article summarizes recent efforts to develop in vitro tests for predicting skin sensitizers. Cell-based assays, in chemico methods and, to a lesser extent, in silico methods are presented together with a discussion of their current status. With considerable progress having been achieved during the last years, the rationale today is that data from different non-animal test methods will have to be combined in order to obtain reliable hazard and potency information on potential skin sensitizers. PMID:22707154

  12. Requirements specification for the sharing sensitive scientific data test bed

    OpenAIRE

    Crompton, S.; Aziz, Benjamin; Wilson, M.; Arenas, A. (A.); Matthews, B

    2008-01-01

    This document describes the Sharing Sensitive Scientific Data test bed. The test bed uses a multi-organisation research project in Structural Biology (SB) to highlight the data sharing requirements in scientific research as gathered from practising scientists and providers of large research facilities in the Science and Technology Facilities Council (STFC).

  13. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part VI. Evaluation of the antimalarial activity of plants used by Isoceño-Guaraní Indians.

    Science.gov (United States)

    Bourdy, G; Oporto, P; Gimenez, A; Deharo, E

    2004-08-01

    Seventy-seven plant extracts (corresponding to 62 different species) traditionally used by the Isoceño-Guaraní, a native community living in the Bolivian Chaco, were screened for antimalarial activity in vitro on Plasmodium falciparum chloroquine sensitive strain (F32), and on ferriprotoporphyrin (FP) IX biocrystallisation inhibition test (FBIT). Among these extracts, seven displayed strong in vitro antimalarial activity, and 25 were active in the FBIT test. Positive results on both tests were recorded for six extracts: Argemone subfusiformis aerial part, Aspidosperma quebracho-blanco bark, Castela coccinea leaves and bark, Solanum argentinum leaves and Vallesia glabra bark. Results are discussed in relation with Isoceño-Guaraní traditional medicine. Further studies to be undertaken in relation with these results are also highlighted. PMID:15234764

  14. Rapid test for assay of ozone sensitivity in Escherichia coli

    International Nuclear Information System (INIS)

    A rapid test devised for assay of ozone sensitivity in Escherichia coli based on the procedure used by Chung and Greenberg (1968) for assay of radiation sensitivity is described. The detection of new mutants, either more resistant or more sensitive than wild type strain to ozone, and the genetic analysis of ozone recombinants are now possible. Results confirm that ozone resistance is probably involved with DNA repair mechanisms; and show that ozone and ultraviolet light inhibit the cell division capacity of lon mutants in a similar way. (orig.)

  15. Pricing, distribution, and use of antimalarial drugs.

    OpenAIRE

    Foster, S. D.

    1991-01-01

    Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much a...

  16. Antimalarial effect of agmatine on Plasmodium berghei K173 strain

    Institute of Scientific and Technical Information of China (English)

    SURui-Bin; WEIXiao-Li; LIUYin; LIJin

    2003-01-01

    AIM: To study the antimalarial effect of agmatine (Agm) on chloroquine-susceptible Plasmodium berghei K173strain (S strain) and the P berghei K173 resistant strain (R strain). METHODS: The antimalarial effects of Agm onP berghei K173 S strain and R strain were evaluated by Peters 4-d suppression test in mice. RESULTS: Agm(12.5-200 mg/kg,ig,daily) decreased the parasitemia for both P berghei K173 S strain (IC50=139 mg/kg) and Rstrain (IC50=126mg/kg) in mice. Subcutaneous injection (sc) of Agm (5-40mg/kg,tid) showed relatively strongerantimalarial effect than intragastric gavage (IC50=30 mg/kg) in P berghei K 173 S strain. Spermidine antagonized theantimalarial effect of Agm for P berghei K173 S strain and R strain. Agm did not reverse the chloroquine resistanceof P berghei K173 S strain, dl-α-Difluoromethylornithine (DFMO, sc) decreased the parasitemia of P BergheiK173 S strain and this effect was antagonized by spermidine. CONCLUSION: Agm has an antimalarial effect andthe mechanism is related to its inhibition of polyamine synthesis.

  17. Beta blockers and the sensitivity of the thallium treadmill test

    International Nuclear Information System (INIS)

    The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies

  18. Sensitivity tests for an ensemble Kalman filter for aerosol assimilation

    OpenAIRE

    N. A. J. Schutgens; T. Miyoshi; Takemura, T.; Nakajima, T

    2010-01-01

    We present sensitivity tests for a global aerosol assimilation system utilizing AERONET observations of AOT (aerosol optical thickness) and AAE (aerosol Ångström exponent). The assimilation system employs an ensemble Kalman filter which requires optimization of three numerical parameters: ensemble size nens, local patch size npatch and inflation factor ρ. In addition, experiments are performed to test ...

  19. Efficient Noninferiority Testing Procedures for Simultaneously Assessing Sensitivity and Specificity of Two Diagnostic Tests

    Directory of Open Access Journals (Sweden)

    Guogen Shan

    2015-01-01

    Full Text Available Sensitivity and specificity are often used to assess the performance of a diagnostic test with binary outcomes. Wald-type test statistics have been proposed for testing sensitivity and specificity individually. In the presence of a gold standard, simultaneous comparison between two diagnostic tests for noninferiority of sensitivity and specificity based on an asymptotic approach has been studied by Chen et al. (2003. However, the asymptotic approach may suffer from unsatisfactory type I error control as observed from many studies, especially in small to medium sample settings. In this paper, we compare three unconditional approaches for simultaneously testing sensitivity and specificity. They are approaches based on estimation, maximization, and a combination of estimation and maximization. Although the estimation approach does not guarantee type I error, it has satisfactory performance with regard to type I error control. The other two unconditional approaches are exact. The approach based on estimation and maximization is generally more powerful than the approach based on maximization.

  20. Antimalarial activity and toxicity of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Ratchanu; Bunyong; Wanna; Chaijaroenkul; Tullayakorn; Plengsuriyakarn; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate the antimalarial activity and toxicity of the crude ethanolic extract of its pericarp both in vitro and in vim.Methods:The antimalarial activity of Gareinja mangostana(G.mangostana)Linn.extract against 3D7 and Kl Plasmodium falciparum(P.falciparum)clone were assessed using SYBR green I-based assay.A 4-day suppressive test of Plasmodium berghei{P.berghei)infected mouse was performed to investigate in vivo antimalarial activity.Results:The in vitro antimalarial activity was seleclive(SI>5?and classified as weak and good lo moderate activity against both 3D7 and K1 P.falciparum,clones with median IC50(range)values of 11.12(10.94-11.29)and 7.54(6.80-7.68)μg/mL,respectively.The extract was considered nontoxic to mice.The maximum tolerated doses for acute and subacute toxicity in mice were 5 000and 2 000 mg/kg,respectively.Median(range)parasite density on day 4 of the negative control group(25%Tween-80),mice treated with 250,500,1000,and 2 000 mg/kg body weight of the extract,and 10 mg/kg body weight of chloroquine for 14 d were 12.8(12.2-13.7),11.4(9.49-13.8),11.6(9.9-12.5),11.7(10.6-12.8),10.9(9.4-11.6)and 0(0-0)%respectively.Parasite density on day 4in the control group treated with Tween-80 was higher than the groups treated with chloroquine and all dose levels of the extract.Conclusions:G.mangostana linn,showed weak antimalarial activity of the extract both in vitro and in vivo could be due to limitation of absorption of the active compounds.

  1. Sensitivity or artifact? -- IQ Toxicity Test -- effluent values

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, K.R.; Novotny, A.N.; Batista, N.

    1995-12-31

    Several complex effluents were DAPHNIA MAGNA IQ TOXICITY TESTED -- (1.25 hours) and conventionally tested with Daphnia magna (48 hours). In many samples the IQ Technology yielded low EC50 values while the 48 hour exposures yielded no acute toxicity. Possible explanations have been suggested for this occurrence such as: genotoxicity, mutagenicity, substrate interference, and enzyme satiation. To identify the causative agent(s) of this response a Toxicity Identification Evaluation was performed on one of the samples. To define the nature of the response, THE SOS-CHROMOTEST KIT and THE MUTA-CHROMOPLATE KIT were utilized to characterize genotoxicity and mutagenicity respectively. The sample did not test positive for genotoxicity but tested positive for mutagenicity only after activation with S9 enzymes, suggesting the presence of promutagens. Additional work needs to be performed to correlate IQ TOXICITY TEST sensitivity with positive MUTA-CHROMOPLATE response.

  2. A database of antimalarial drug resistance

    Directory of Open Access Journals (Sweden)

    Ringwald Pascal

    2006-06-01

    Full Text Available Abstract A large investment is required to develop, license and deploy a new antimalarial drug. Too often, that investment has been rapidly devalued by the selection of parasite populations resistant to the drug action. To understand the mechanisms of selection, detailed information on the patterns of drug use in a variety of environments, and the geographic and temporal patterns of resistance is needed. Currently, there is no publically-accessible central database that contains information on the levels of resistance to antimalaria drugs. This paper outlines the resources that are available and the steps that might be taken to create a dynamic, open access database that would include current and historical data on clinical efficacy, in vitro responses and molecular markers related to drug resistance in Plasmodium falciparum and Plasmodium vivax. The goal is to include historical and current data on resistance to commonly used drugs, like chloroquine and sulfadoxine-pyrimethamine, and on the many combinations that are now being tested in different settings. The database will be accessible to all on the Web. The information in such a database will inform optimal utilization of current drugs and sustain the longest possible therapeutic life of newly introduced drugs and combinations. The database will protect the valuable investment represented by the development and deployment of novel therapies for malaria.

  3. Antimalarial activity of some Colombian medicinal plants.

    Science.gov (United States)

    Garavito, G; Rincón, J; Arteaga, L; Hata, Y; Bourdy, G; Gimenez, A; Pinzón, R; Deharo, E

    2006-10-11

    Antimalarial activity of 10 vegetal extracts (9 ethanolic extracts and 1 crude alkaloid extract), obtained from eight species traditionally used in Colombia to treat malaria symptoms, was evaluated in culture using Plasmodium falciparum chloroquine resistant (FcB2) strain and in vivo on rodent malaria Plasmodium berghei. The activity on ferriprotoporphyrin biomineralization inhibition test (FBIT) was also assessed. Against Plasmodium falciparum, eight extracts displayed good activity Abuta grandifolia (Mart.) Sandwith (Menispermaceae) leaves, Acacia farnesiana (L.) Willd. (Mimosaceae) leaves, Acnistus arborescens (L.) Schltdl. (Solanaceae) aerial part, Croton leptostachyus Kunth (Euphorbiaceae) aerial part, Piper cumanense Kunth (Piperaceae) fruits and leaves, Piper holtonii C. DC. (Piperaceae) aerial part and Xylopia aromatica (Lam.) Mart. (Annonaceae) bark with IC(50) values ranging from <1 to 2.1 microg/ml, while in the in vivo model only Abuta grandifolia alkaloid crude extract exhibits activity, inhibiting 66% of the parasite growth at 250 mg/kg/day. In the FBIT model, five extracts were active (Abuta grandifolia, Croton leptostachyus, Piper cumanense fruit and leaves and Xylopia aromatica). PMID:16713157

  4. Testing of new hypoxic cell sensitizers in vivo

    International Nuclear Information System (INIS)

    We tested five agents as potential sensitizers of hypoxic cells in vivo in mammary tumors in C3H mice in comparison with misonidazole. The LD/sub 50/2/ for desmethylmisonidazole was 2.7 mg/g body wt, compared to 1.3 for misonidazole. It was as effective in reducing the TCD50 of MDAH-MCa-4 as were equitoxic doses of misonidazole. the LD/sub 50/2/ of SR-2508 was 3.3 mg/g and was as effective a sensitizer as misonidazole. Ro 07-0741 was more toxic, with an LD/sub 50/2/ of 0.6 mg/g, but was as effective as misonidazole at equitoxic doses. NP-1 was also more toxic than misonidazole (LA/sub 50/2/ = 04 mg/g) but was a less effective sensitizer. Rotenone, which causes sensitization by inhibiting cellular respiration, thus increasing the diffusion distance of oxygen, was extremely toxic (LD/sub 50/2/ - 0.003 mg/g), and systemic respiratory inhibition and the radioprotective effects of the dimethyl sulfoxide used to dissolve it rendered it totally ineffective as a sensitizer in vivo

  5. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

    Directory of Open Access Journals (Sweden)

    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT. The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85% and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%, drug stores (14%, mobile providers (4% and grocery stores (2%. Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61% and private (42% sectors. Conclusions While data on the anti-malarial

  6. Testing the Perturbation Sensitivity of Abortion-Crime Regressions

    OpenAIRE

    Michał Brzeziński; Maria Halber

    2012-01-01

    The hypothesis that the legalisation of abortion contributed significantly to the reduction of crime in the United States in 1990s is one of the most prominent ideas from the recent “economics-made-fun” movement sparked by the book Freakonomics. This paper expands on the existing literature about the computational stability of abortion-crime regressions by testing the sensitivity of coefficients’ estimates to small amounts of data perturbation. In contrast to previous studies, we use a new da...

  7. Resistance of Plamodium falciparum to Antimalarial Drugs in Zaragoza (Antioquia, Colombia, 1998

    Directory of Open Access Journals (Sweden)

    Silvia Blair-Trujillo

    2002-04-01

    Full Text Available Plasmodium falciparum sensitivity to chloroquine (CHL, amodiaquine (AMO and sulfadoxine/pyrimethamine (SDX/PYR was assessed in vivo and in vitro in a representative sample from the population of Zaragoza in El Bajo Cauca region (Antioquia-Colombia. There were 94 patients with P. falciparum evaluated. For the in vivo test the patients were followed by clinical examination and microscopy, during 7 days. The in vitro test was performed following the recommendations of the World Health Organization. The in vivo prevalence of resistance to CHL was 67%, to AMO 3% and to SDX/PYR 9%. The in vitro test showed sensitivity to all antimalarials evaluated. Concordance for CHL between the in vivo and in vitro tests was 33%. For AMO and SDX/PYR, the concordance was 100%. We conclude that a high percentage of patients are resistant to CHL (in vivo. A high rate of intestinal parasitism might explain in part, the differences observed between the in vivo and the in vitro results. Therefore, new policies and treatment regimens should be proposed for the treatment of the infection in the region. Nationwide studies assessing the degree of resistance are needed.

  8. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Norazsida Ramli

    2014-01-01

    Full Text Available Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral toxicity dose at 5000 mg/kg was conducted to evaluate the safety of this extract. Twenty mice were divided into control and experimental group. All the mice were observed for signs of toxicity, mortality, weight changes and histopathological changes. Antimalarial activity of different extract doses of 50, 200, 400 and 1000 mg/kg were tested in vivo against Plasmodium berghei infections in mice (five mice for each group during early, established and residual infections. Results: The acute oral toxicity test revealed that no mortality or evidence of adverse effects was seen in the treated mice. The extract significantly reduced the parasitemia by the 50 (P = 0.000, 200 (P = 0.000 and 400 mg/kg doses (P = 0.000 in the in vivo prophylactic assay. The percentage chemo-suppression was calculated as 83.33% for 50 mg/kg dose, 75.62% for 200 mg/kg dose and 90.74% for 400 mg/kg dose. Body weight of all treated groups; T1, T2, T3 and T4 also showed enhancement after 7 days posttreatment. Statistically no reduction of parasitemia calculated for curative and suppressive test. Conclusion: Thus, this extract may give a promising agent to be used as a prophylactic agent of P. berghei infection.

  9. Sensitivity of Peach Bottom turbine trip test calculations using RETRAN

    International Nuclear Information System (INIS)

    Fast acting power increase transients are required to test the one-dimensional reactor kinetics used in RETRAN. In addition, methods used to model the steam separator, down comer, steam lines and feedback from turbine control valves, feedwater and recirculation flow control can be tested using the Peach Bottom benchmarks. Gulf States Utilities (GSU) performed simulations of the three Peach Bottom turbine trip tests. These calculations were performed using RETRAN02/MOD4, with kinetics data generated by the GSU's CASMO1/SIMULATE-E/SIMTRAN models. The Peach Bottom tests were held at low power conditions for which reactor vessel pressure and enthalpy distribution data was unavailable. During the computer program benchmark process, it was found that the results showed a large sensitivity to the reactor conditions used to initialize RETRAN. Many other sensitivities were observed such as turbine trip induced pressure wave impact on overall results. Timing and magnitude of the pressure waves were found to be affected by the use of equilibrium or non-equilibrium models, by distribution of separator inertia and by distribution of pressure losses through core and separators. The timing and magnitude of these pressure waves has a significant effect on the peak power and heat flux

  10. Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

    Directory of Open Access Journals (Sweden)

    Zaloumis Sophie

    2012-08-01

    Full Text Available Abstract Background Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic-pharmacodynamic (PK-PD model for predicting within-host parasite response was performed. Methods Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the parasite life cycle, and the parasite multiplication factor due to asexual reproduction. The model also included the maximal killing rate of each drug, and the blood drug concentration associated with half of that killing effect (in vivo EC50, derived from the in vitro IC50, the extent of binding to 0.5% Albumax present in the in vitro testing media, and the drugs plasma protein binding and whole blood to plasma partitioning ratio. All stochastic simulations were performed using a Latin-Hypercube-Sampling approach. Results The simulations demonstrated that the proportion of patients cured was highly sensitive to the in vivo EC50 and the maximal killing rate of the partner drug co-administered with the artemisinin derivative. The in vivo EC50 values that corresponded to on average 95% of patients cured were much higher than the adjusted values derived from the in vitro IC50. The proportion clinically cured was not strongly influenced by changes in the parameters defining the age distribution of the initial parasite burden (mean age of 4 to 16 hours and the parasite multiplication factor every life cycle (ranging from 8 to 12 fold/cycle. The median parasite clearance times, however, lengthened as the standard deviation of the initial parasite burden increased (i

  11. Responding to the challenge of antimalarial drug resistance by routine monitoring to update national malaria treatment policies

    DEFF Research Database (Denmark)

    Vestergaard, Lasse S; Ringwald, Pascal

    2007-01-01

    of rational and updated malaria treatment policies, but defining and updating such policies requires a sufficient volume of high-quality drug-resistance data collected at national and regional levels. Three main tools are used for drug resistance monitoring, including therapeutic efficacy tests, in......Reduced sensitivity of Plasmodium falciparum to formerly recommended cheap and well-known antimalarial drugs places an increasing burden on malaria control programs and national health systems in endemic countries. The high costs of the new artemisinin-based combination treatments underline the use...... additional information about changing patterns of resistance. However, some of the tests are technically demanding, and thus there is a need for more resources for training and capacity building in endemic countries to be able to adequately respond to the challenge of drug resistance....

  12. Recent developments in naturally derived antimalarials: cryptolepine analogues.

    Science.gov (United States)

    Wright, Colin W

    2007-06-01

    Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues. PMID:17637183

  13. 78 FR 68076 - Request for Information on Alternative Skin Sensitization Test Methods and Testing Strategies and...

    Science.gov (United States)

    2013-11-13

    ...The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is developing a U.S. plan for the evaluation of alternative skin sensitization test methods and testing strategies. The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) requests information that ICCVAM might use to develop this plan and......

  14. Substandard anti-malarial drugs in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Sie Ali

    2008-05-01

    Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

  15. Odor-Specific Loss of Smell Sensitivity with Age as Revealed by the Specific Sensitivity Test.

    Science.gov (United States)

    Seow, Yi-Xin; Ong, Peter K C; Huang, Dejian

    2016-07-01

    The perception of odor mixtures plays an important role in human food intake, behavior, and emotions. Decline of smell acuity with normal aging could impact food perception and preferences at various ages. However, since the landmark Smell Survey by National Geographic, little has been elucidated on differences in the onset and extent of loss in olfactory sensitivity toward single odorants. Here, using the Specific Sensitivity test, we show the onset and extent of loss in both identification and detection thresholds of odorants with age are odorant-specific. Subjects of Chinese descent in Singapore (186 women, 95 men), aged 21-80 years, were assessed for olfactory sensitivity of 10 odorants from various odor groups. Notably, subjects in their 70s required 179 times concentration of rose-like odorant (2-phenylethanol) than subjects in the 20s, while thresholds for onion-like 2-methyloxolane-3-thiol only differed by 3 times between the age groups. In addition, identification rate for 2-phenylethanol was negatively correlated with age throughout adult life whereas mushroom-like oct-1-en-3-ol was equally identified by subjects across all ages. Our results demonstrated the girth of differentiated olfactory loss due to normal ageing, which potentially affect overall perception and preferences of odor mixtures with age. PMID:27001718

  16. The ACTwatch project: methods to describe anti-malarial markets in seven countries

    Directory of Open Access Journals (Sweden)

    Chapman Steven

    2011-10-01

    Full Text Available Abstract Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT and malaria diagnostics including rapid diagnostic tests (RDTs. To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the

  17. New 1-Aryl-3-Substituted Propanol Derivatives as Antimalarial Agents

    Directory of Open Access Journals (Sweden)

    Antonio Monge

    2009-10-01

    Full Text Available This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 μM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria.

  18. Epidemiological models for the spread of anti-malarial resistance

    Directory of Open Access Journals (Sweden)

    Antia R

    2003-02-01

    Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

  19. Expanding the Antimalarial Drug Arsenal—Now, But How?

    Directory of Open Access Journals (Sweden)

    Rajeev K. Mehlotra

    2011-04-01

    Full Text Available The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii repurposing drugs that are currently used to treat other infections or diseases; (iii chemically modifying existing antimalarial compounds; (iv exploring natural sources; (v large-scale screening of diverse chemical libraries; and (vi through parasite genome-based (“targeted” discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum, and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs, and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now and “long term” (5. Next generation of

  20. Test Patterns to Determine Sensitivity and Resolution of Scintigraphy

    International Nuclear Information System (INIS)

    The quality of a scintigram is one of the most important factors governing the diagnostic value of scintigraphy. The quality of a scintigram is not only decided by the instrumentation, techniques of scintigraphy and the kinds and amounts of radiopharmaceuticals administered, but is also influenced by the distribution of radionuclides in a target organ and its surroundings. All these factors are so complicated that it is difficult to analyse the quality of a scintigram and to make comparisons by simple methods. The quality of a scintigram is usually expressed by three parameters: resolution, sensitivity and background contribution. These parameters can be relatively easily determined by analysing the scintigrams of the selected test patterns which are composed of three-dimensional arrangements of radioactive sources particularly designed for this purpose. This fact has been proved by several hundred scan experiments performed with many phantoms and test patterns. The result suggests that the particular combination of line sources arranged on a plane and the particular forms of plane sources piled up to a block can be applied as useful test patterns. (author)

  1. Testing the Perturbation Sensitivity of Abortion-Crime Regressions

    Directory of Open Access Journals (Sweden)

    Michał Brzeziński

    2012-06-01

    Full Text Available The hypothesis that the legalisation of abortion contributed significantly to the reduction of crime in the United States in 1990s is one of the most prominent ideas from the recent “economics-made-fun” movement sparked by the book Freakonomics. This paper expands on the existing literature about the computational stability of abortion-crime regressions by testing the sensitivity of coefficients’ estimates to small amounts of data perturbation. In contrast to previous studies, we use a new data set on crime correlates for each of the US states, the original model specifica-tion and estimation methodology, and an improved data perturbation algorithm. We find that the coefficients’ estimates in abortion-crime regressions are not computationally stable and, therefore, are unreliable.

  2. Disk diffusion sensitivity testing and antibacterial activity of azithromycin.

    Science.gov (United States)

    Davila, D; Tambić, T; Djokić, S; Kolacny-Babić, L

    1992-02-01

    Azithromycin (CAS 83905-01-5) disks with the selected loading (10, 15, 20 micrograms) were used for determination of the most suitable azithromycin disk concentration. Estimation was carried out by means of the regression line related to the zone size inhibition. Testing was performed on a variety of freshly isolated gram-positive, gram-negative and anaerobic bacteria derived from various specimens collected from patients. Using the disk diffusion method with 10 micrograms of azithromycin per disk in total 431 gram-positive, 875 gram-negative bacterial strains and 59 anaerobic bacteria were analysed. It was concluded that azithromycin disk containing 10 micrograms is sufficient for determination of bacterial sensitivity. PMID:1319164

  3. On the use of sensitivity tests in seismic tomography

    Science.gov (United States)

    Rawlinson, N.; Spakman, W.

    2016-05-01

    Sensitivity analysis with synthetic models is widely used in seismic tomography as a means for assessing the spatial resolution of solutions produced by, in most cases, linear or iterative nonlinear inversion schemes. The most common type of synthetic reconstruction test is the so-called checkerboard resolution test in which the synthetic model comprises an alternating pattern of higher and lower wave speed (or some other seismic property such as attenuation) in 2-D or 3-D. Although originally introduced for application to large inverse problems for which formal resolution and covariance could not be computed, these tests have achieved popularity, even when resolution and covariance can be computed, by virtue of being simple to implement and providing rapid and intuitive insight into the reliability of the recovered model. However, checkerboard tests have a number of potential drawbacks, including (1) only providing indirect evidence of quantitative measures of reliability such as resolution and uncertainty, (2) giving a potentially misleading impression of the range of scale-lengths that can be resolved, and (3) not giving a true picture of the structural distortion or smearing that can be caused by the data coverage. The widespread use of synthetic reconstruction tests in seismic tomography is likely to continue for some time yet, so it is important to implement best practice where possible. The goal of this paper is to develop the underlying theory and carry out a series of numerical experiments in order to establish best practice and identify some common pitfalls. Based on our findings, we recommend (1) the use of a discrete spike test involving a sparse distribution of spikes, rather than the use of the conventional tightly spaced checkerboard; (2) using data coverage (e.g. ray-path geometry) inherited from the model constrained by the observations (i.e. the same forward operator or matrix), rather than the data coverage obtained by solving the forward problem

  4. Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana

    Directory of Open Access Journals (Sweden)

    M. El-Duah & K. Ofori-Kwakye

    2012-09-01

    Full Text Available Background & objectives: The artemisinin-based antimalarial medicines are first line medicines in the treatmentof severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in variouscountries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and qualityof selected brands of artemisinin-based antimalarial medicines marketed in Ghana.Methods: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P and licensedchemical shops (LCSs in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layerchromatography were employed in determining the authenticity of the samples. Important quality assessmenttests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of activepharmaceutical ingredients (APIs were determined.Results: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of masstest while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strengthtest. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength anddisintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs.The other 13 artemisinin products contained either a lower (underdose or higher (overdose amount of thespecified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemicalshops.Interpretation & conclusion: All the artemisinin-based medicines tested (except AL1 were of substandardquality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalentin Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development

  5. The Hug-up Test: A New, Sensitive Diagnostic Test for Supraspinatus Tears

    Institute of Scientific and Technical Information of China (English)

    Yu-Lei Liu; Ying-Fang Ao; Hui Yan; Guo-Qing Cui

    2016-01-01

    Background:The supraspinatus tendon is the most commonly affected tendon in rotator cufftears.Early detection ofa supraspinatus tear using an accurate physical examination is,therefore,important.However,the currently used physical tests for detecting supraspinatus tears are poor diagnostic indicators and involve a wide range of sensitivity and specificity values.Therefore,the aim of this study was to establish a new physical test for the diagnosis of supraspinatus tears and evaluate its accuracy in comparison with conventional tests.Methods:Between November 2012 and January 2014,200 consecutive patients undergoing shoulder arthroscopy were prospectively evaluated preoperatively.The hug-up test,empty can (EC) test,full can (FC) test,Neer impingement sign,and Hawkins-Kennedy impingement sign were used and compared statistically for their accuracy in terms of supraspinatus tears,with arthroscopic findings as the gold standard.Muscle strength was precisely quantified using an electronic digital tensiometer.Results:The prevalence of supraspinatus tears was 76.5%.The hug-up test demonstrated the highest sensitivity (94.1%),with a low negative likelihood ratio (NLR,0.08) and comparable specificity (76.6%) compared with the other four tests.The area under the receiver operating characteristic curve for the hug-up test was 0.854,with no statistical difference compared with the EC test (z =1.43 8,P =0.075) or the FC test (z =1.498,P =0.067).The hug-up test showed no statistical difference in terms of detecting different tear patterns according to the position (x2 =0.578,P =0.898) and size (Fisher's exact test,P > 0.999) compared with the arthroscopic examination.The interobserver reproducibility of the hug-up test was high,with a kappa coefficient of 0.823.Conclusions:The hug-up test can accurately detect supraspinatus tears with a high sensitivity,comparable specificity,and low NLR compared with the conventional clinical tests and could,therefore,improve the

  6. Sensitivity study on hydraulic well testing inversion using simulated annealing

    International Nuclear Information System (INIS)

    For environmental remediation, management of nuclear waste disposal, or geothermal reservoir engineering, it is very important to evaluate the permeabilities, spacing, and sizes of the subsurface fractures which control ground water flow. Cluster variable aperture (CVA) simulated annealing has been used as an inversion technique to construct fluid flow models of fractured formations based on transient pressure data from hydraulic tests. A two-dimensional fracture network system is represented as a filled regular lattice of fracture elements. The algorithm iteratively changes an aperture of cluster of fracture elements, which are chosen randomly from a list of discrete apertures, to improve the match to observed pressure transients. The size of the clusters is held constant throughout the iterations. Sensitivity studies using simple fracture models with eight wells show that, in general, it is necessary to conduct interference tests using at least three different wells as pumping well in order to reconstruct the fracture network with a transmissivity contrast of one order of magnitude, particularly when the cluster size is not known a priori. Because hydraulic inversion is inherently non-unique, it is important to utilize additional information. The authors investigated the relationship between the scale of heterogeneity and the optimum cluster size (and its shape) to enhance the reliability and convergence of the inversion. It appears that the cluster size corresponding to about 20--40 % of the practical range of the spatial correlation is optimal. Inversion results of the Raymond test site data are also presented and the practical range of spatial correlation is evaluated to be about 5--10 m from the optimal cluster size in the inversion

  7. [Historical overview of antimalarials used in Venezuela].

    Science.gov (United States)

    Zerpa de Artiles, N

    1993-06-01

    A historical review of antimalarials used in Venezuela is presented from the time when the bark of quina was used until the massive distribution of quinine and metoquine by the Dirección de Malariología y Saneamiento Ambiental. The utility of chloroquine and primaquine against sensible parasite isolates and of sulfadoxine-pyrimethamine and quinine, currently used against P. falciparum resistant strains, is thoroughly discussed. The author suggests use of artemisimine and its derivatives as a very promising antimalarial drug. She also stresses the possibility of the application of new antimalaria vaccine against P. falciparum blood states, presently assayed in the country as an additional tool in malaria control programs. PMID:11640680

  8. The antimalarial ferroquine: from bench to clinic

    Directory of Open Access Journals (Sweden)

    Biot C.

    2011-08-01

    Full Text Available Ferroquine (FQ, SSR97193 is currently the most advanced organometallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocenecontaining compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.

  9. Potential antimalarial activity of indole alkaloids

    OpenAIRE

    Frederich, Michel; Tits, Monique; Angenot, Luc

    2008-01-01

    New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This ...

  10. Antimalarial drug resistance and combination chemotherapy.

    OpenAIRE

    White, N.

    1999-01-01

    Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the cha...

  11. Pricing, distribution, and use of antimalarial drugs.

    Science.gov (United States)

    Foster, S D

    1991-01-01

    Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much as half of antimalarials distributed in many developing countries. Use of antimalarials through the health services is often poor; drug shortages are common and overprescription and overuse of injections are significant problems. Anxiety over drug costs may prevent patients from getting the necessary treatment for malaria, especially because of the seasonal appearance of this disease when people's cash reserves are very low. The high costs may lead them to unofficial sources, which will sell a single tablet instead of a complete course of treatment, and subsequently to increased, often irrational demand for more drugs and more injections. Increasingly people are resorting to self-medication for malaria, which may cause delays in seeking proper treatment in cases of failure, especially in areas where chloroquine resistance has increased rapidly. Self-medication is now widespread, and measures to restrict the illicit sale of drugs have been unsuccessful. The "unofficial" channels thus represent an unacknowledged extension of the health services in many countries; suggestions are advanced to encourage better self-medication by increasing the knowledge base among the population at large (mothers, schoolchildren, market sellers, and shopkeepers), with an emphasis on correct dosing and on the importance of seeking further treatment without delay, if necessary. PMID:1893512

  12. Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response.

    Science.gov (United States)

    Veiga, Maria Isabel; Osório, Nuno S; Ferreira, Pedro Eduardo; Franzén, Oscar; Dahlstrom, Sabina; Lum, J Koji; Nosten, Francois; Gil, José Pedro

    2014-12-01

    Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance. PMID:25267670

  13. Probing the antimalarial mechanism of artemisinin and OZ277 (arterolane) with nonperoxidic isosteres and nitroxyl radicals.

    Science.gov (United States)

    Fügi, Matthias A; Wittlin, Sergio; Dong, Yuxiang; Vennerstrom, Jonathan L

    2010-03-01

    Peroxidic antimalarials such as the semisynthetic artemisinins are critically important in the treatment of drug-resistant malaria. Nevertheless, their peroxide bond-dependent mode of action is still not well understood. Using combination experiments with cultured Plasmodium falciparum cells, we investigated the interactions of the nitroxide radical spin trap, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and four of its analogs with artemisinin and the ozonide drug development candidate OZ277. The antagonism observed for combinations of artemisinin or OZ277 with the TEMPO analogs supports the hypothesis that the formation of carbon-centered radicals is critical for the activity of these two antimalarial peroxides. The TEMPO analogs showed a trend toward greater antagonism with artemisinin than they did with OZ277, an observation that can be explained by the greater tendency of artemisinin-derived carbon-centered radicals to undergo internal self-quenching reactions, resulting in a lower proportion of radicals available for subsequent chemical reactions such as the alkylation of heme and parasite proteins. In a further mechanistic experiment, we tested both artemisinin and OZ277 in combination with their nonperoxidic analogs. The latter had no effect on the antimalarial activities of the former. These data indicate that the antimalarial properties of peroxides do not derive from reversible interactions with parasite targets. PMID:20028825

  14. In vitro antimalarial activity of extracts of some plants from a biological reserve in Costa Rica.

    Science.gov (United States)

    Chinchilla, Misael; Valerio, Idalia; Sánchez, Ronald; Mora, Víctor; Bagnarello, Vanessa; Martínez, Laura; Gonzalez, Antonieta; Vanegas, Juan Carlos; Apestegui, Alvaro

    2012-06-01

    Treatment with the usual antimalarial drugs, have induced parasite resistance, reinforcing the need to finding natural antimalarial components that would be found on plants from the forest. Therefore, we decided to look for these components in Costa Rican plants from a protected forest area. Fresh and dry extracts of roots, bark, leaves, flowers and fruits of 25 plants from a biological reserve in Costa Rica, Reserva Biol6gica Alberto Manuel Brenes (REBAMB), were studied in vitro for the presence of substances with antimalarial activity. By studying the inhibition of P berghei schizogony, we assessed the antimalarial activity of several plant extracts: Aphelandra aurantiaca, A. tridentata (Acanthaceae); Xanthosoma undipes (Araceae); Iriartea deltoidea (Arecaceae); Neurolaena lobata (Asteraceae); Senna papillosa, Pterocarpus hayessi, Lonchocarpus pentaphyllus (Fabaceae); Nectandra membranacea, Persea povedae, Cinamomum chavarrianum (Lauraceae); Hampea appendiculata (Malvaceae); Ruagea glabra, Guarea glabra (Meliaceae); Psidium guajava (Myrtaceae); Bocconia frutescens (Papaveraceae); Piper friedrichsthalii (Piperaceae); Clematis dioica (Ranunculaceae); Prunus annularis (Rosaceae); Siparuna thecaphora (Siparunaceae); Solanum arboreum, Witheringia solanacea (Solanaceae); Ticodendrum incognitum (Ticodendraceae); Heliocarpus appendiculatus (Tiliaceae) and Myriocarpa longipes (Urticaceae). We used different parts of the plants as well as fresh and dried extracts for testing IC50. The solid content of the extracts ranged from 1-71.9 microg/mL. The fresh extracts showed stronger activity than the dry ones. Since the plants showing the strongest antimalarial activity are very common in Central America, and some similar genera of these plants have shown positives results in South America, we considered important to present these findings for discussion. On the other hand, this is the first systematic study of this kind ever realized in a circumscribed and protected area of

  15. Bilayer Effects of Antimalarial Compounds.

    Directory of Open Access Journals (Sweden)

    Nicole B Ramsey

    Full Text Available Because of the perpetual development of resistance to current therapies for malaria, the Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process. We tested the 80 most potent compounds from the box for bilayer-mediated effects on membrane protein conformational changes (a measure of likely toxicity in a gramicidin-based stopped flow fluorescence assay. Among the Malaria Box compounds tested, four compounds altered membrane properties (p< 0.05; MMV007384 stood out as a potent bilayer-perturbing compound that is toxic in many cell-based assays, suggesting that testing for membrane perturbation could help identify toxic compounds. In any case, MMV007384 should be approached with caution, if at all.

  16. Natural polyhydroxyalkanoate–gold nanocomposite based biosensor for detection of antimalarial drug artemisinin

    International Nuclear Information System (INIS)

    The worrisome trend of antimalarial resistance has already highlighted the importance of artemisinin as a potent antimalarial agent. The current investigation aimed at fabricating a biosensor based on natural polymer polyhydroxyalkanoate–gold nanoparticle composite mounting on an indium-tin oxide glass plate for the analysis of artemisinin. The biosensor was fabricated using an adsorbing horse-radish peroxidase enzyme on the electrode surface for which cyclic voltammetry was used to monitor the electro-catalytic reduction of artemisinin under diffusion controlled conditions. Electrochemical interfacial properties and immobilization of enzyme onto a polyhydroxyalkanoate–gold nanoparticle film were evaluated, and confirmed by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. The differential pulse voltammetric peak current for artemisinin was increased linearly (concentration range of 0.01–0.08 μg mL−1) with sensitivity of 0.26 μA μg mL−1. The greater sensitivity of the fabricated biosensor to artemisinin (optimum limits of detection were 0.0035 μg mL−1 and 0.0036 μg mL−1 in bulk and spiked human serum, respectively) could be of much aid in medical diagnosis. - Highlights: • Extraction of PHA from indigenously isolated Pseudomonas aeruginosa BPC2 • Developed PHA/AuNPs/HRP/ITO based biosensor without the use of chemical cross linker • Detection of antimalarial drug artemisinin using the nanocomposite based biosensor

  17. Natural polyhydroxyalkanoate–gold nanocomposite based biosensor for detection of antimalarial drug artemisinin

    Energy Technology Data Exchange (ETDEWEB)

    Phukon, Pinkee [Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam (India); Radhapyari, Keisham [Analytical Chemistry Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam (India); Konwar, Bolin Kumar [Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam (India); Nagaland University (Central), Lumami, Zunheboto, Nagaland 798627 (India); Khan, Raju, E-mail: khan.raju@gmail.com [Analytical Chemistry Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam (India)

    2014-04-01

    The worrisome trend of antimalarial resistance has already highlighted the importance of artemisinin as a potent antimalarial agent. The current investigation aimed at fabricating a biosensor based on natural polymer polyhydroxyalkanoate–gold nanoparticle composite mounting on an indium-tin oxide glass plate for the analysis of artemisinin. The biosensor was fabricated using an adsorbing horse-radish peroxidase enzyme on the electrode surface for which cyclic voltammetry was used to monitor the electro-catalytic reduction of artemisinin under diffusion controlled conditions. Electrochemical interfacial properties and immobilization of enzyme onto a polyhydroxyalkanoate–gold nanoparticle film were evaluated, and confirmed by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. The differential pulse voltammetric peak current for artemisinin was increased linearly (concentration range of 0.01–0.08 μg mL{sup −1}) with sensitivity of 0.26 μA μg mL{sup −1}. The greater sensitivity of the fabricated biosensor to artemisinin (optimum limits of detection were 0.0035 μg mL{sup −1} and 0.0036 μg mL{sup −1} in bulk and spiked human serum, respectively) could be of much aid in medical diagnosis. - Highlights: • Extraction of PHA from indigenously isolated Pseudomonas aeruginosa BPC2 • Developed PHA/AuNPs/HRP/ITO based biosensor without the use of chemical cross linker • Detection of antimalarial drug artemisinin using the nanocomposite based biosensor.

  18. Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial chemotype.

    Science.gov (United States)

    Santos, Sofia A; Lukens, Amanda K; Coelho, Lis; Nogueira, Fátima; Wirth, Dyann F; Mazitschek, Ralph; Moreira, Rui; Paulo, Alexandra

    2015-09-18

    A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity. The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, we were able to identify a new compound (10d) with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC50 values ∼ 3 μM), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs. PMID:26295174

  19. The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2003-09-01

    Full Text Available Abstract Background The naturally occurring benzoquinone ansamycin compound, geldanamycin (GA, is a specific inhibitor of heat shock protein 90 (Hsp90 and is a potential anticancer agent. Since Plasmodium falciparum has been reported to have an Hsp90 ortholog, we tested the possibility that GA might inhibit it and thereby display antiparasitic activity. Results We provide direct recombinant DNA evidence for the Hsp90 protein of Plasmodium falciparum, the causative agent of fatal malaria. While the mRNA of Hsp90 was mainly expressed in ring and trophozoite stages, the protein was found in all stages, although schizonts contained relatively lower amounts. In vitro the parasitic Hsp90 exhibited an ATP-binding activity that could be specifically inhibited by GA. Plasmodium growth in human erythrocyte culture was strongly inhibited by GA with an IC50 of 20 nM, compared to the IC50 of 15 nM for chloroquine (CQ under identical conditions. When used in combination, the two drugs acted synergistically. GA was equally effective against CQ-sensitive and CQ-resistant strains (3D7 and W2, respectively and on all erythrocytic stages of the parasite. Conclusions Together, these results suggest that an active and essential Hsp90 chaperone cycle exists in Plasmodium and that the ansamycin antibiotics will be an important tool to dissect its role in the parasite. Additionally, the favorable pharmacology of GA, reported in human trials, makes it a promising antimalarial drug.

  20. Sensitivity of Routine Tests for Urine Protein to Hemoglobin

    OpenAIRE

    Jansen, Barbara S.; Lumsden, John H.

    1985-01-01

    Increasing concentrations of canine hemoglobin were added to aliquots of urine and saline to determine the relative sensitivity of several hemoglobin and protein detection methods including commercial reagent strips and sulfosalicylic acid. The hemoglobin detection pads of the reagent strips were 50 times more sensitive than the protein detection pads, indicating the presence of hemoglobin at a concentration of 0.001 g/L whereas the protein pads did not react positively unless the hemoglobin ...

  1. The prevalence and degree of resistance of Plasmodium falciparum to first-line antimalarial drugs: an in vitro study from a malaria endemic region in Yemen

    International Nuclear Information System (INIS)

    Unpublished studies on antimalarial drug efficacy have found low levels of chloroquine resistance in Yemen. This study was carried out to determine the current prevalence of drug resistance in Plasmodium falciparum in Yemen to the main anti-malarial drugs and to determine the effective concentration (EC) values. The WHO standard protocol was used for the selection of subjects, collection of blood samples, culture techniques, examination of post-culture blood slides and interpretation of results. The in vitro micro-test Mark III was used for assessing susceptibility of P. falciparum isolates. The criteria for blood parasite density was met by 219 P. falciparum malaria patients. Chloroquine resistance was found in 47% of isolated P. falciparum schizonts. Mefloquine resistance was found in 5.2%. In addition, the EC50 and EC95 values in blood that inhibited schizont maturation in resistant isolates were higher than the normal therapeutic level for mefloquine. No resistance occurred against quinine or artemisinin, with no growth at the cut off level for quinine and inhibition at low concentrations of artemisinin. Our study confirmed the occurrence of chloroquine-resistant P. falciparum and a slow increase in the rate of this resistance will increase further and spread over all the foci of malaria in Yemen. The low rate of chloroquine-resistant P. falciparum was lower than that reported in Africa or Southeast Asia, but is the first report of the mefloquine resistance in Yemen. Finally, the isolates were sensitive to low concentrations of quinine and artemisinin. (author)

  2. Antimalarial Activity of Ultra-Short Peptides

    Directory of Open Access Journals (Sweden)

    María Yolanda Rios

    2009-12-01

    Full Text Available Ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. On the basis of the IC50 data for these compounds, the effects of nature, polarity, and amino acid sequence on Plasmodium berghei schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4 and Lys-Phe-Phe-Orn (5 showed a very important activity with IC50 values of 3.31 and 2.57 μM, respectively. These two tetrapeptides are candidates for subsequent in vivo assays and SARS investigations.

  3. [Recent development in animal testing to predict the skin and respiratory sensitizing potential of chemicals].

    Science.gov (United States)

    Aoyama, Kohji

    2010-01-01

    The identification of chemicals with skin and/or respiratory sensitizing potential is important for the prevention of allergic diseases in both living and work environments. Although a number of animal models for respiratory allergic diseases have been reported, none of these models meets the goals of broad assessments of chemical sensitizing potential. We are attempting to develop a test for predicting the respiratory sensitization of chemicals. In the evaluation of skin sensitization of chemicals, the mostly used predictive tests are the guinea pig maximization test, Buehler test, and mouse local lymph node assay (LLNA). However, only LLNA has been validated formally and independently. Recent studies have revealed that EC3 estimated by LLNA correlates well with human skin sensitizing potency and the threshold for the induction of skin sensitization in the human repeat patch test. Thus, LLNA can predict the potency of skin sensitizing potential of a chemical and its risk in humans. PMID:20134104

  4. In vitro antimalarial activity and cytotoxicity of cochlospermum tinctorium and C. planchonii leaf extracts and essential oils.

    Science.gov (United States)

    Benoit-Vical, F; Valentin, A; Mallié, M; Bastide, J M; Bessière, J M

    1999-05-01

    The antimalarial and toxicological properties of Cochlospermum tinctorium and C. planchonii extracts and essential oils prepared from their leaves were studied. The oil components were extracted by hydrodistillation of the plant leaves and characterized by gas chromatography and mass spectrometry. Crude extracts and oils were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between the oils and the parasite culture, and ranged from 22 to 500 micrograms/ml. C. planchonii leaf oil yielded the best antimalarial effect (IC50: 22-35 micrograms/ml), while the most potent effect from crude leaf extracts was induced by C. tinctorium. The cytotoxicity of the leaf crude extracts and oils was assessed on the K562 cell line and showed IC50 values ranging between 33 and 2000 micrograms/ml. PMID:10364849

  5. Detection of In Vitro Antimalarial Activity of Some Myanmar Medicinal Plants

    International Nuclear Information System (INIS)

    In order to find out the novel effective antimalarials. six medicinal plants, namely Erythrina stricta Roxb. (Kathit), Luffa acutangula Roxb. (Thabut - Kja), Cordia rothii Roem. and Schult. (Thanet), Tribulus terrestris Linn. (Sule). Zizphus oenoplia Mill. (Paung - pe) and Mimusops elengi Roxb. (Khaye) were selected and tested for their antimalarial activity by using in vitro microdilution technique. According to the in vitro test results, Erythrina stricta Roxb. (Kathit) was found to possess significant suppressive effect on Plasmodium falciparum. With the serially diluted extract dosage concentrations ranging from 1.250 ng/ml to 40,000 ng/ml, the schizont suppressive percentage of Eryhrina stricta Roxb. (Kathi) was observed to be 19.57%, 35.44%, 55.18%, 96.04%,100% and 100% respectively

  6. Discovery of Novel Liver-Stage Antimalarials through Quantum Similarity.

    Directory of Open Access Journals (Sweden)

    David J Sullivan

    Full Text Available Without quantum theory any understanding of molecular interactions is incomplete. In principal, chemistry, and even biology, can be fully derived from non-relativistic quantum mechanics. In practice, conventional quantum chemical calculations are computationally too intensive and time consuming to be useful for drug discovery on more than a limited basis. A previously described, original, quantum-based computational process for drug discovery and design bridges this gap between theory and practice, and allows the application of quantum methods to large-scale in silico identification of active compounds. Here, we show the results of this quantum-similarity approach applied to the discovery of novel liver-stage antimalarials. Testing of only five of the model-predicted compounds in vitro and in vivo hepatic stage drug inhibition assays with P. berghei identified four novel chemical structures representing three separate quantum classes of liver-stage antimalarials. All four compounds inhibited liver-stage Plasmodium as a single oral dose in the quantitative PCR mouse liver-stage sporozoites-challenge model. One of the newly identified compounds, cethromycin [ABT-773], a macrolide-quinoline hybrid, is a drug with an extensive (over 5,000 people safety profile warranting its exploitation as a new weapon for the current effort of malaria eradication. The results of our molecular modeling exceed current state-of-the-art computational methods. Drug discovery through quantum similarity is data-driven, agnostic to any particular target or disease process that can evaluate multiple phenotypic, target-specific, or co-crystal structural data. This allows the incorporation of additional pharmacological requirements, as well as rapid exploration of novel chemical spaces for therapeutic applications.

  7. Chitosan-based nanocarriers for antimalarials

    Science.gov (United States)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Bende, A.; Borodi, Gh.; Bratu, I.

    2012-02-01

    The objective of this research was to synthesize and characterize chitosan-based liquid and solid materials with unique absorptive and mechanical properties as carriers for quinine - one of the most used antimalarial drug. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare solid release systems as sponges is presented. The preparation by double emulsification of CTS hydrogels carrying quinine as anti-malarial drug is reported. The concentration of quinine in the CTS hydrogel was 0.08 mmol. Chitosan - drug loaded hydrogel was used to generate solid sponges by freeze-drying at -610°C and 0.09 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), spectrofluorimetry, differential scanning calorimetry (DSC) and X-ray diffractometry. The results indicated that the drug molecule is forming temporary chelates in CTS hydrogels and sponges. Electron paramagnetic resonance (EPR) demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan - drug supramolecular cross-linked assemblies.

  8. Effect of antimalarial drug primaquine and its derivatives on the ionization potential of hemoglobin: A QM/MM study

    OpenAIRE

    Liu, Haining; Ding, Yuanqing; Walker, Larry A.; Doerksen, Robert J

    2013-01-01

    We used quantum mechanics/molecular mechanics calculations to test if antimalarial primaquine (PQ) and its derivatives aid the conversion of hemoglobin to methemoglobin by binding to hemoglobin and merely lowering hemoglobin’s ionization potential (IP). Our results showed that PQ and its derivatives do not significantly lower the hemoglobin IP, disproving the hypothesis.

  9. Antimalarial and cytotoxic properties of Chukrasia tabularis A. Juss and Turraea vogelii Hook F. Ex. Benth.

    Science.gov (United States)

    Ogbole, Omonike O; Saka, Yusuf A; Fasinu, Pius S; Fadare, Adenike A; Ajaiyeoba, Edith O

    2016-04-01

    Malaria, caused by plasmodium parasite, is at the moment the highest cause of morbidity and mortality in the tropics. Recently, there is increasing efforts to develop more potent antimalarials from plant sources that will have little or no adverse effects. This study is aimed at investigating the in vivo mice antimalarial and in vitro antiplasmodial effects of two Meliaceae plants commonly used in Nigerian ethnomedicine as part of recipe for treating malaria infection: Chukrasia tabularis and Turraea vogelii. Hot water decoction and methanol extract of both plants were evaluated for their antimalarial activity in vivo using the mice model assay and in vitro using the parasite lactate dehydrogenase (pLDH) assay. The extracts were also assessed for toxicity with brine shrimp lethality assay and in mammalian cell lines using the neural red assay. The in vivo mice model antimalarial study showed that the methanol extract of the stem bark of C. tabularis exhibited the highest % chemosuppression (83.65 ± 0.66) at the highest dosage administered (800 mg/kg) when compared with chloroquine diphosphate, the standard reference drug which had a % suppression of 90.36 ± 0.04 (p < 0.05). The in vitro antiplasmodial study indicated that the aqueous extract of the stem bark of C. tabularis displayed good activity against Plasmodium falciparum chloroquine-sensitive (D6) strain (IC50 of 10.739 μg/mL) and chloroquine-resistant (W2) strain. Chloroquine and artemisinin had <0.163 and <0.0264, respectively. PMID:26911147

  10. Sensitivity and specificity of the nickel spot (dimethylglyoxime) test

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Skare, Lizbet; Lundgren, Lennart; Menné, Torkil; Johansen, Jeanne D; Maibach, Howard I; Lidén, Carola

    2010-01-01

    The accuracy of the dimethylglyoxime (DMG) nickel spot test has been questioned because of false negative and positive test reactions. The EN 1811, a European standard reference method developed by the European Committee for Standardization (CEN), is fine-tuned to estimate nickel release around the...

  11. Skin sensitization--a critical review of predictive test methods in animals and man.

    Science.gov (United States)

    Botham, P A; Basketter, D A; Maurer, T; Mueller, D; Potokar, M; Bontinck, W J

    1991-04-01

    With the exception of the Draize Test, the guinea-pig test methods currently accepted by regulatory authorities worldwide are well able to predict the potential of a material to cause skin sensitization. Nevertheless, (a) some methods are more sensitive than others (e.g. adjuvant tests are generally more sensitive than non-adjuvant tests); (b) methods cannot be sufficiently standardized to give full reproducibility of results between laboratories; and (c) most methods are based on subjective visual grading of skin reactions--difficulties thus arise when testing coloured or irritant materials. Laboratories must be able to show the sensitivity of the method(s) they use by demonstrating that positive reactions occur with mild/moderate contact allergens rather than the strong/extreme sensitizers currently recommended in certain guidelines, specifically in the EEC Test Method. The sensitivity of the adjuvant tests is such that it is possible to halve the minimum number of animals required by present regulatory guidelines without compromising the capacity of the tests to detect weak/mild sensitizers. A similar review has not yet been made for non-adjuvant tests. Alternative test methods, including some recently developed mouse models, offer several advantages, including more objective endpoints. These tests have not been extensively validated and this precludes their use at present for regulatory purposes other than to confirm the sensitization potential of a material. Two new test methods using mice, the Mouse Ear-swelling Test and the Local Lymph Node Assay, appear promising. They should undergo rigorous interlaboratory testing to determine their sensitivity and specificity. In vitro methods do not represent a viable alternative in the foreseeable future. An approach using quantitative structure-activity relationships is the most likely route to a non-animal model, but this will require considerable research, development and validation. Human sensitization tests have

  12. Screening of the antimalarial activity of plants of the Cucurbitaceae family

    Directory of Open Access Journals (Sweden)

    Cláudia Zuany Amorim

    1991-01-01

    Full Text Available Crude ethanolic extracts (CEEs from two species of Cucurbitaceae, Cucurbita maxima and Momordica charantia (commonly called "abóbora moranga" and melão de São Caetano", respectively were assayed for antimalarial activity by the 4-d suppressive test. The CEE of dry C. maxima seeds showed strong antimalarial activity following oral administration (259 and 500 mg/kg, reducing by 50% the levels of parasistemia in Plasmodium berghey-infected mice. Treatment of normal animals with 500 mg/Kg of the extract three days before intravenous injection of P. berghei caused a significant 30% reduction in parasitemic levels. No effect was observed when the animals were treated with the CEE only on the day of inoculation. Oral administration of the CEE of dry M. charantia leaves adminstered orally was ineffective up to 500 mg/Kg in lowering the parasitemic levels of malarious mice.

  13. In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants

    Directory of Open Access Journals (Sweden)

    Valter F de Andrade-Neto

    2007-06-01

    Full Text Available In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae, the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae, respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae, all presented significant in vitro inhibition (more active than quinine and chloroquine of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.

  14. Sensitivity Analysis of OECD Benchmark Tests in BISON

    Energy Technology Data Exchange (ETDEWEB)

    Swiler, Laura Painton [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gamble, Kyle [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmidt, Rodney C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Williamson, Richard [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    This report summarizes a NEAMS (Nuclear Energy Advanced Modeling and Simulation) project focused on sensitivity analysis of a fuels performance benchmark problem. The benchmark problem was defined by the Uncertainty Analysis in Modeling working group of the Nuclear Science Committee, part of the Nuclear Energy Agency of the Organization for Economic Cooperation and Development (OECD ). The benchmark problem involv ed steady - state behavior of a fuel pin in a Pressurized Water Reactor (PWR). The problem was created in the BISON Fuels Performance code. Dakota was used to generate and analyze 300 samples of 17 input parameters defining core boundary conditions, manuf acturing tolerances , and fuel properties. There were 24 responses of interest, including fuel centerline temperatures at a variety of locations and burnup levels, fission gas released, axial elongation of the fuel pin, etc. Pearson and Spearman correlatio n coefficients and Sobol' variance - based indices were used to perform the sensitivity analysis. This report summarizes the process and presents results from this study.

  15. Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance ofPlasmodium falciparum isolates to antimalarial drugs

    Institute of Scientific and Technical Information of China (English)

    Raewadee Wisedpanichkij; Wanna Chaicharoenkul; Poonuch Mahamad; Prapichaya Prompradit; Kesara Na-Bangchang

    2010-01-01

    Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH)levels, glutathione reductase(PfGR)and glutathione S-transferase (PfGST) genes and sensitivity ofPlasmodium falciparum (P. falciparum)isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods: A total of70P. falciparum isolates were collected from endemic areas of multi-drug resistance (Tak, Chantaburi and Ranong Provinces) during the year2008-2009. The in vitro assessment of antimalarial activity ofP. falciparumclones (K1- and Dd2 chloroquine resistant and3D7-chloroquine sensitive) and isolates to chloroquine, quinine, mefloquine and arteusnate was performed based onSYBR Green modified assay.Results:68 (97.14%), 11 (15.71%) and28 (40%) isolates respectively were classified as chloroquine-, quinine- and mefloquine-resistant isolates. With this limited number ofP. falciparum isolates included in the analysis, no significant association between amplification ofPfGST gene and sensitivity of the parasite to chloroquine, quinine, mefloquine and quinine was found. Based onPCR analysis,Dd2, K1 and3D7clones all contained only one copy of thePfGST gene. All isolates (70) also carried only one copy number of PfGST gene. There appears to be an association between amplification ofPfGR gene and chloroquine resistance. The3D7and Dd2 clones were found to carry only onePfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions: Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in theGSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.

  16. Radiation damage test of position sensitive silicon detectors

    International Nuclear Information System (INIS)

    A study of radiation damage of position sensitive silicon detectors (PSDs), for use as a position monitor of high energy heavy ion beams, was carried out. It is revealed that the position linearity of the standard PSD is strongly affected even by an absorbed dose around 100 Gy. The reason of the distortion of position linearity was considered to be a positive charge build-up in the SiO2 layer covering the PSD. To overcome the problem, new types of PSDs have been developed raising impurity density in the resistive layer and removing the SiO2 layer. A PSD with a distortion of less than 100 μm over an effective area of 13 mm x 13 mm is obtained which is usable as a heavy ion beam monitor. (orig.)

  17. Artemisinin anti-malarial drugs in China.

    Science.gov (United States)

    Guo, Zongru

    2016-03-01

    Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. PMID:27006895

  18. Antimalarial activity of selected Sudanese medicinal plants with emphasis to Maytenus senegalensis

    International Nuclear Information System (INIS)

    The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity against 3D7 with IC50 values ≤ 50 μ g/ml. While 21 extracts (57%) showed antimalrial activities with IC50 values ≤ 50 μ g/ml on Dd2. 13 extracts (22%) and ten extracts (18%) only showed an activity with IC50 values ≤ 5 μ g/ml on 3 D7 and Dd2, respectively. The activities of some plant extracts, which affected 3D7 strain, were measured using the radiolabelled (3H) hypoxanthine method and microscopical count. 15 plant extracts (48%) from 32 showed IC50 values ≤ 50 μ g/ml against 3D7 strain using the radiolabelled hypoxanthine methods and only 5 extracts (16%) showed IC50 values ≤ 5 μ g/ml against 3D7. Most of the extracts screened had a low effect on lymphocyte proliferation (IC50 values >100 μ g/ml), where as Sonochous cornatus, Balanites aegyptiaca, Tamarindus indica, Acacia nilotica, Annona squamosa, Eucalyptus globulus and Cassia tora enhanced lymphocyte proliferation. liquid-liquid partition of methanolic preparation of Acacia nilotica seeds and husk showed that the ethylacetate phase possessed the highest activity against both 3D7 and Dd2 strains

  19. Synthesis and evaluation of antimalarial activity of curcumin derivatives

    International Nuclear Information System (INIS)

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC50 values ranging from 1.7 to 15.2 μg mL-1), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  20. NEW ANTIMICROBIAL SENSITIVITY TESTS OF BIOFILM OF STREPTOCOCCUS MUTANS IN ARTIFICIAL MOUTH MODEL

    Institute of Scientific and Technical Information of China (English)

    李鸣宇; 汪俊; 刘正; 朱彩莲

    2004-01-01

    Objective To develop a new antimicrobial sensitivity test model for oral products in vitro.Methods A biofilm artificial mouth model for antimicrobial sensitivity tests was established by modifying the LKI chromatography chamber. Using sodium fluoride and Tea polyphenol as antimicrobial agent and Streptococcus mutans as target, sensitivity tests were studied. Results The modeling biofilm assay resulted in a MIC of 1.28mg/ml for fluoride against S. mutans, which was 32 times the MIC for broth maco-dilution method. The differential resistance of bacteria bioflim to antimicrobial agent relative to planktonic cells was also demonstrated. Conclusion The biofilm artificial mouth model may be useful in oral products test.

  1. Antimalarial activity of plumbagin in vitro and in animal models

    OpenAIRE

    Sumsakul, Wiriyaporn; Plengsuriyakarn, Tullayakorn; Chaijaroenkul, Wanna; Viyanant, Vithoon; Karbwang, Juntra; Na-Bangchang, Kesara

    2014-01-01

    Background Plumbagin is the major active constituent in several plants including Plumbago indica Linn. (root). This compound has been shown to exhibit a wide spectrum of biological and pharmacological activities. The present study aimed to evaluate the in vitro and in vivo antimalarial activity of plumbagin including its acute and subacute toxicity in mice. Methods In vitro antimalarial activity of plumbagin against K1 and 3D7 Plasmodium falciparum clones were assessed using SYBR Green I base...

  2. Antimalarial Synergy of Cysteine and Aspartic Protease Inhibitors

    OpenAIRE

    Semenov, Andrey; Olson, Jed E.; Rosenthal, Philip J.

    1998-01-01

    It has been proposed that the Plasmodium falciparum cysteine protease falcipain and aspartic proteases plasmepsin I and plasmepsin II act cooperatively to hydrolyze hemoglobin as a source of amino acids for erythrocytic parasites. Inhibitors of each of these proteases have potent antimalarial effects. We have now evaluated the antimalarial effects of combinations of cysteine and aspartic protease inhibitors. When incubated with cultured P. falciparum parasites, cysteine and aspartic protease ...

  3. Towards optimal design of anti-malarial pharmacokinetic studies.

    OpenAIRE

    White Nicholas J; Price Ric N; Jamsen Kris M; Simpson Julie A; Lindegardh Niklas; Tarning Joel; Duffull Stephen B

    2009-01-01

    Abstract Background Characterization of anti-malarial drug concentration profiles is necessary to optimize dosing, and thereby optimize cure rates and reduce both toxicity and the emergence of resistance. Population pharmacokinetic studies determine the drug concentration time profiles in the target patient populations, including children who have limited sampling options. Currently, population pharmacokinetic studies of anti-malarial drugs are designed based on logistical, financial and ethi...

  4. The role of anti-malarial drugs in eliminating malaria.

    OpenAIRE

    White, NJ

    2008-01-01

    Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and tran...

  5. The role of anti-malarial drugs in eliminating malaria

    OpenAIRE

    White Nicholas J

    2008-01-01

    Abstract Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia...

  6. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    OpenAIRE

    Ramli, Norazsida; Ahamed, Pakeer Oothuman Syed; Elhady, Hassan Mohamed; Taher, Muhammad

    2014-01-01

    Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral t...

  7. Expanding the Antimalarial Drug Arsenal—Now, But How?

    OpenAIRE

    MEHLOTRA, RAJEEV K.; Grimberg, Brian T

    2011-01-01

    The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, th...

  8. In Vitro Antimalarial Activity of Novel Semisynthetic Nocathiacin I Antibiotics

    OpenAIRE

    Sharma, Indu; Sullivan, Margery; McCutchan, Thomas F.

    2015-01-01

    Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in...

  9. Vancomycin sensitivity and koh string test as an alternative to gram staining of bacteria

    OpenAIRE

    Arthi K; Appalaraju B; Parvathi S

    2003-01-01

    Two hundred and eighteen bacterial isolates obtained from various clinical samples were subjected to Gram stain by conventional method. For all the isolates potassium hydroxide (KOH) string test and sensitivity to vancomycin were done. Gram positive bacteria showed 100% sensitivity to vancomycin as also 100% negativity for string test. Of the gram negative bacteria, 99.42% were resistant to vancomycin while 98.85% were positive for the string test. KOH and vancomyc...

  10. Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia.

    Science.gov (United States)

    Yeung, Shunmay; Lawford, Harriet L S; Tabernero, Patricia; Nguon, Chea; van Wyk, Albert; Malik, Naiela; DeSousa, Mikhael; Rada, Ouk; Boravann, Mam; Dwivedi, Prabha; Hostetler, Dana M; Swamidoss, Isabel; Green, Michael D; Fernandez, Facundo M; Kaur, Harparkash

    2015-06-01

    Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources. PMID:25897063

  11. Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV tests.

    Directory of Open Access Journals (Sweden)

    Kristen L Hess

    Full Text Available New rapid point-of-care (POC tests are being developed that would offer the opportunity to increase screening and treatment of several infections, including syphilis. This study evaluated three of these new rapid POC tests at a site in Southern California.Participants were recruited from a testing center in Long Beach, California. A whole blood specimen was used to evaluate the performance of the Dual Path Platform (DPP Syphilis Screen & Confirm, DPP HIV-Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons were Treponema pallidum passive particle agglutination (TPPA, rapid plasma reagin (RPR, HCV enzyme immunoassay (EIA, and HIV-1/2 EIA.A total of 948 whole blood specimens were analyzed in this study. The sensitivity of the HIV tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity and specificity of the HCV test were 91.8% and 99.3%, respectively. The treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the Screen & Confirm test improved to 90.0% when cases who were both treponemal and nontreponemal positive were compared to TPPA+/RPR ≥ 1 ∶ 8.The HIV and HCV on the multi-infection tests showed good performance, but the treponemal and nontreponemal tests had low sensitivity. These results could be due to a low prevalence of active syphilis in the sample population because the sensitivity improved when the gold standard was limited to those more likely to be active cases. Further evaluation of the new syphilis POC tests is required before implementation into testing programs.

  12. Temporal evolution of the sensitivity determined during the extrinsic uniformity test on two gamma cameras

    International Nuclear Information System (INIS)

    One of the suggestions in the new Protocol (February 2010) of the European Association of Nuclear Medicine Routine quality control recommendations for nuclear medicine instrumentation is to record the value cps / MBq obtained in carrying out this test to track sensitivity thus obtained. Ideally, this sensitivity should remain constant over time. At our institution this parameter has been registered since February 2009. In this paper we analyze data collected through December 2010 (23 months), relating the apparent loss of sensitivity downtime losses.

  13. Parametric Sensitivity Tests—European Polymer Electrolyte Membrane Fuel Cell Stack Test Procedures

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    As fuel cells are increasingly commercialized for various applications, harmonized and industry-relevant test procedures are necessary to benchmark tests and to ensure comparability of stack performance results from different parties. This paper reports the results of parametric sensitivity tests...

  14. Improved sensitivity testing of explosives using transformed Up-Down methods

    International Nuclear Information System (INIS)

    Sensitivity tests provide data that help establish guidelines for the safe handling of explosives. Any sensitivity test is based on assumptions to simplify the method or reduce the number of individual sample evaluations. Two common assumptions that are not typically checked after testing are 1) explosive response follows a normal distribution as a function of the applied stimulus levels and 2) the chosen test level spacing is close to the standard deviation of the explosive response function (for Bruceton Up-Down testing for example). These assumptions and other limitations of traditional explosive sensitivity testing can be addressed using Transformed Up-Down (TUD) test methods. TUD methods have been developed extensively for psychometric testing over the past 50 years and generally use multiple tests at a given level to determine how to adjust the applied stimulus. In the context of explosive sensitivity we can use TUD methods that concentrate testing around useful probability levels. Here, these methods are explained and compared to Bruceton Up-Down testing using computer simulation. The results show that the TUD methods are more useful for many cases but that they do require more tests as a consequence. For non-normal distributions, however, the TUD methods may be the only accurate assessment method.

  15. Estimating sensitivity of laboratory testing for influenza in Canada through modelling.

    Directory of Open Access Journals (Sweden)

    Dena L Schanzer

    Full Text Available BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV, adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32-34%, varying from 30-40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza.

  16. Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

    DEFF Research Database (Denmark)

    Kielsgaard Kristensen, Thomas; Vestergaard, Hanne; Bindslev-Jensen, Carsten; Møller, Michael Boe; Broesby-Olsen, Sigurd

    2014-01-01

    The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order to...... establish its value in clinical use. We therefore evaluated sensitive KIT D816V mutation analysis of PB as a diagnostic test in an entire case-series of adults with mastocytosis. We demonstrate for the first time that by using a sufficiently sensitive KIT D816V mutation analysis, it is possible to detect...... the mutation in PB in nearly all adult mastocytosis patients. The mutation was detected in PB in 78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients (75%). The test was 100% specific as determined by analysis of clinically relevant control patients who all tested negative...

  17. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    OpenAIRE

    A.M. Valença; A.E. Nardi; Nascimento, I.; W.A. Zin; M. Versiani

    2002-01-01

    The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in...

  18. LOW-LEVEL MALARIA INFECTIONS DETECTED BY A SENSITIVE POLYMERASE CHAIN REACTION ASSAY AND USE OF THIS TECHNIQUE IN THE EVALUATION OF MALARIA VACCINES IN AN ENDEMIC AREA

    OpenAIRE

    Imoukhuede, Egeruan B; Andrews, Laura; Milligan, Paul; Berthoud, Tamara; Bojang, Kalifa; Nwakanma, Davis; Ismaili, Jamila; Buckee, Caroline; Njie, Fanta; KEITA, SAIKOU; Sowe, Maimuna; Lang, Trudie; Gilbert, Sarah C.; Greenwood, Brian M.; Hill, Adrian V. S.

    2007-01-01

    The feasibility of using a sensitive polymerase chain reaction (PCR) to evaluate malaria vaccines in small group sizes was tested in 102 adult Gambian volunteers who received either the malaria vaccine regimen FP9 ME-TRAP/MVA ME-TRAP or rabies vaccine. All volunteers received the antimalarial drugs primaquine and Lapdap plus artesunate to eliminate malaria parasites. Volunteers in a further group received an additional single treatment with sulfadoxine-pyrimethamine (SP) to prevent new infect...

  19. Bioluminometric assay of ATP in mouse brain: Determinant factors for enhanced test sensitivity

    Indian Academy of Sciences (India)

    Haseeb Ahmad Khan

    2003-06-01

    Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the analysis of ATP in small tissue samples. The results showed that the sensitivity of the FLB test can be enhanced several fold by using ultraturax homogenizer, perchloric acid extraction, neutralization of acid extract and its optimal dilution, before performing the assay reaction.

  20. Maternal sensitivity and language in early childhood: a test of the transactional model.

    Science.gov (United States)

    Leigh, Patricia; Nievar, M Angela; Nathans, Laura

    2011-08-01

    This study examined the relation between mothers' sensitive responsiveness to their children and the children's expressive language skills during early childhood. Reciprocal effects were tested with dyads of mothers and their children participating in the National Institute of Health and Human Development Study of Early Child Care and Youth Development. Sensitive maternal interactions positively affected children's later expressive language in the second and third years of life. Although maternal sensitivity predicted later language skills in children, children's language did not affect later maternal sensitivity as indicated in a structural equation model. These results do not support the 1975 transactional model of child development of Sameroff and Chandler. A consistent pattern of sensitivity throughout infancy and early childhood indicates the importance of fostering maternal sensitivity in infancy for prevention or remediation of expressive language problems in young children. PMID:21987927

  1. Use and quality of antimalarial drugs in the private sector in Viet Nam.

    OpenAIRE

    Cong, L D; Yen, P. T.; Nhu, T. V.; Binh, L N

    1998-01-01

    This study examines the use and quality of antimalarial drugs in the growing private sector of Viet Nam. The practices of drug vendors (called alternative treatment providers (ATPs)) as well as their stocks and the quality of drugs sold by them, and the local production and distribution of antimalarials were investigated. Antimalarials were sold by the vast majority of ATPs, almost all the common antimalarials being available for sale. The practices and indications for sale, however, varied. ...

  2. Targeting the Plasmodium vivax equilibrative nucleoside transporter 1 (PvENT1 for antimalarial drug development

    Directory of Open Access Journals (Sweden)

    Roman Deniskin

    2016-04-01

    Full Text Available Infection with Plasmodium falciparum and vivax cause most cases of malaria. Emerging resistance to current antimalarial medications makes new drug development imperative. Ideally a new antimalarial drug should treat both falciparum and vivax malaria. Because malaria parasites are purine auxotrophic, they rely on purines imported from the host erythrocyte via Equilibrative Nucleoside Transporters (ENTs. Thus, the purine import transporters represent a potential target for antimalarial drug development. For falciparum parasites the primary purine transporter is the P. falciparum Equilibrative Nucleoside Transporter Type 1 (PfENT1. Recently we identified potent PfENT1 inhibitors with nanomolar IC50 values using a robust, yeast-based high throughput screening assay. In the current work we characterized the Plasmodium vivax ENT1 (PvENT1 homologue and its sensitivity to the PfENT1 inhibitors. We expressed a yeast codon-optimized PvENT1 gene in Saccharomyces cerevisiae. PvENT1-expressing yeast imported both purines ([3H]adenosine and pyrimidines ([3H]uridine, whereas wild type (fui1Δ yeast did not. Based on radiolabel substrate uptake inhibition experiments, inosine had the lowest IC50 (3.8 μM, compared to guanosine (14.9 μM and adenosine (142 μM. For pyrimidines, thymidine had an IC50 of 183 μM (vs. cytidine and uridine; mM range. IC50 values were higher for nucleobases compared to the corresponding nucleosides; hypoxanthine had a 25-fold higher IC50 than inosine. The archetypal human ENT1 inhibitor 4-nitrobenzylthioinosine (NBMPR had no effect on PvENT1, whereas dipyridamole inhibited PvENT1, albeit with a 40 μM IC50, a 1000-fold less sensitive than human ENT1 (hENT1. The PfENT1 inhibitors blocked transport activity of PvENT1 and the five known naturally occurring non-synonymous single nucleotide polymorphisms (SNPs with similar IC50 values. Thus, the PfENT1 inhibitors also target PvENT1. This implies that development of novel

  3. Does sensitivity measured from screening test-sets predict clinical performance?

    Science.gov (United States)

    Soh, BaoLin P.; Lee, Warwick B.; Mello-Thoms, Claudia R.; Tapia, Kriscia A.; Ryan, John; Hung, Wai Tak; Thompson, Graham J.; Heard, Rob; Brennan, Patrick C.

    2014-03-01

    Aim: To examine the relationship between sensitivity measured from the BREAST test-set and clinical performance. Background: Although the UK and Australia national breast screening programs have regarded PERFORMS and BREAST test-set strategies as possible methods of estimating readers' clinical efficacy, the relationship between test-set and real life performance results has never been satisfactorily understood. Methods: Forty-one radiologists from BreastScreen New South Wales participated in this study. Each reader interpreted a BREAST test-set which comprised sixty de-identified mammographic examinations sourced from the BreastScreen Digital Imaging Library. Spearman's rank correlation coefficient was used to compare the sensitivity measured from the BREAST test-set with screen readers' clinical audit data. Results: Results shown statistically significant positive moderate correlations between test-set sensitivity and each of the following metrics: rate of invasive cancer per 10 000 reads (r=0.495; p DCIS per 10 000 reads (r=0.444; p < 0.01). Conclusion: Comparison between sensitivity measured from the BREAST test-set and real life detection rate demonstrated statistically significant positive moderate correlations which validated that such test-set strategies can reflect readers' clinical performance and be used as a quality assurance tool. The strength of correlation demonstrated in this study was higher than previously found by others.

  4. Are somatosensory evoked potentials of the tibial nerve the most sensitive test in diagnosing multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Djuric S

    2010-01-01

    Full Text Available Background : Multiple sclerosis (MS is mostly diagnosed clinically, but the diagnosis has significantly improved through the use of brain magnetic resonance imaging (MRI, testing of cerebrospinal fluid, and multimodal evoked potentials (MEPs. Even though MRI is the superior method in diagnosing this illness, MEPs remain important because they can detect clinically silent lesions in the sensory and motor pathways of the central nervous system (CNS. Aim : The aim of the study is to test the diagnostic sensitivity of MEPs and MRI and the ratio of their sensitivity in patients with MS. Materials and Methods : The study subjects included 293 patients with MS with disease duration of two to six years: 249 patients with relapsing-remitting (RR MS and 44 with primary-progressive (PP MS. All patients were subjected to an MRI brain scan, visual evoked potentials (VEPs, median somatosensory evoked potentials (SEPs, tibial somatosensory evoked potentials (SEPs, and auditory evoked potentials (AEPs. Abnormal Findings Included : changed wave morphology, interside difference in wave amplitude, absolute and interwave latency increased by 2.5 SD as compared with the control group. The control group comprised of 35 healthy subjects. Results : In this study the most abnormal findings were tibial SEPs, median SEPs, and VEPs. Our results suggest different sensitivity of MEPs in patients suffering from different forms of MS. In RR-MS the sensitivity of tibial SEPs was statically significant (Fischer′s exact probability test as compared to other evoked potential modalities. Similarly VEPs were more sensitive as compared to AEPs. In the PP-MS, median SEPs have been found to be more sensitive than VEPs, while tibial SEPs have been found to be more sensitive than AEPs. There was no significant difference in the sensitivity of MRI and MEPs both the forms of MS. Conclusion : Tibial SEPs produce the most abnormal results and the highest sensitivity in the RR-MS. We

  5. Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract

    Directory of Open Access Journals (Sweden)

    E. O. Ajaiyeoba

    2013-01-01

    Full Text Available Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1 in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μg/mL (7.4 μM and could be a lead for anti-malarial drug discovery.

  6. From hybrid compounds to targeted drug delivery in antimalarial therapy.

    Science.gov (United States)

    Oliveira, Rudi; Miranda, Daniela; Magalhães, Joana; Capela, Rita; Perry, Maria J; O'Neill, Paul M; Moreira, Rui; Lopes, Francisca

    2015-08-15

    The discovery of new drugs to treat malaria is a continuous effort for medicinal chemists due to the emergence and spread of resistant strains of Plasmodium falciparum to nearly all used antimalarials. The rapid adaptation of the malaria parasite remains a major limitation to disease control. Development of hybrid antimalarial agents has been actively pursued as a promising strategy to overcome the emergence of resistant parasite strains. This review presents the journey that started with simple combinations of two active moieties into one chemical entity and progressed into a delivery/targeted system based on major antimalarial classes of drugs. The rationale for providing different mechanisms of action against a single or additional targets involved in the multiple stages of the parasite's life-cycle is highlighted. Finally, a perspective for this polypharmacologic approach is presented. PMID:25913864

  7. Antimalarial activity of Ageratum conyzoides in combination with chloroquine and artesunate

    Institute of Scientific and Technical Information of China (English)

    Ukwe Chinwe V; Ekwunife Obinna I; Epueke Ebele A; Ubaka Chukwuemeka M

    2010-01-01

    Objective: To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides (A. conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice. Methods: Using malaria (Plasmodium berghei) infected albino mice of both sexes, aqueous extracts of A. conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity, respectively. Four-day suppressive test and Rane's curative test were carried out. Results: Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations. Suppressive activities of both extract-drug combinations were greater than the individual drugs alone. Extract-chloroquine (100:5) produced the highest suppressive effect (98% suppression). Curative tests showed absolute survival in two extract-drug combinations. Two extract-drug combinations produced higher curative effects than the individual drugs alone. The highest dose combinations of extract-chloroquine (100:5) and extract-artesunate (100:5) produced absolute parasitemia clearance (cure) in the infected mice. Conclusions: The study indicated that aqueous extract of A. conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice. It contributes a lot in the malaria endemic and poverty stricken tropics.

  8. In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

    Directory of Open Access Journals (Sweden)

    Schleiferböck S

    2013-11-01

    Full Text Available Sarah Schleiferböck,1,2 Christian Scheurer,1,2 Masataka Ihara,3,4 Isamu Itoh,3,4 Ian Bathurst,5,† Jeremy N Burrows,5 Pascal Fantauzzi,5 Julie Lotharius,5 Susan A Charman,6 Julia Morizzi,6 David M Shackleford,6 Karen L White,6 Reto Brun,1,2 Sergio Wittlin1,21Swiss Tropical and Public Health Institute, Basel, 2University of Basel, Basel, Switzerland; 3Drug Discovery Science Research Center, Hoshi University, Shinagawa, Tokyo, Japan; 4Synstar Japan Co, Ltd, Odawara, Japan; 5Medicines for Malaria Venture, Geneva, Switzerland; 6Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia †Ian Bathurst passed away on 26 June 2011Abstract: The objective of this work was to characterize the in vitro (Plasmodium falciparum and in vivo (Plasmodium berghei activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.Keywords: antimalarial studies, cross-resistance, stage-specificity, Plasmodium falciparum

  9. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  10. A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity.

    Science.gov (United States)

    Decosterd, L A; Hoffmann, E; Kyburz, R; Bray, D; Hostettmann, K

    1991-12-01

    The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system. PMID:1818346

  11. Identifying and characterizing chemical skin sensitizers without animal testing: Colipa's research and method development program.

    Science.gov (United States)

    Aeby, P; Ashikaga, T; Bessou-Touya, S; Schepky, A; Gerberick, F; Kern, P; Marrec-Fairley, M; Maxwell, G; Ovigne, J-M; Sakaguchi, H; Reisinger, K; Tailhardat, M; Martinozzi-Teissier, S; Winkler, P

    2010-09-01

    The sensitizing potential of chemicals is usually identified and characterized using one of the available animal test methods, such as the mouse local lymph node assay. Due to the increasing public and political concerns regarding the use of animals for the screening of new chemicals, the Colipa Skin Tolerance Task Force collaborates with and/or funds research groups to increase and apply our understanding of the events occurring during the acquisition of skin sensitization. Knowledge gained from this research is used to support the development and evaluation of novel alternative approaches for the identification and characterization of skin sensitizing chemicals. At present one in chemico (direct peptide reactivity assay (DPRA)) and two in vitro test methods (cell based assays (MUSST and h-CLAT)) have been evaluated within Colipa inter-laboratory ring trials and accepted by the European Centre for the Validation of Alternative Methods (ECVAM) for pre-validation. Data from all three test methods will be used to support the development of testing strategy approaches for skin sensitizer potency prediction. The replacement of the need for animal testing for skin sensitization risk assessment is viewed as ultimately achievable and the next couple of years should set the timeline for this milestone. PMID:20624454

  12. Antimalarial activity of extracts of Malaysian medicinal plants.

    Science.gov (United States)

    Najib Nik A Rahman, N; Furuta, T; Kojima, S; Takane, K; Ali Mohd, M

    1999-03-01

    In vitro and in vivo studies revealed that Malaysian medicinal plants, Piper sarmentosum, Andrographis paniculata and Tinospora crispa produced considerable antimalarial effects. Chloroform extract in vitro did show better effect than the methanol extract. The chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (Andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 h of the same plant spesies. In vivo activity of Andrographis paniculata also demonstrated higher antimalarial effect than other two plant species. PMID:10363840

  13. Comparison of sensitivity of quantiferon-tb gold test and tuberculin skin test in active pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Objective: To compare the sensitivity of tuberculin skin test (TST) and quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. Study Design: Analytical study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2011 to January 2012. Methodology: QuantiFERON-TB gold test (QFT-G) was evaluated and compared it with tuberculin skin test (TST) in 50 cases of active pulmonary tuberculosis, in whom tuberculous infection was suspected on clinical, radiological and microbiological grounds. Sensitivity was determined against positive growth for Mycobacterium tuberculosis. Results: Out of 50 cases, 43 were females and 7 were males. The mean age was 41.84 A+- 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%. Conclusion: QFT-G has much higher sensitivity than TST for active pulmonary tuberculosis. It is unaffected by prior BCG administration and prior exposure to atypical mycobacteria. A positive QFT-G result can be an adjunct to diagnosis in patients having clinical and radiological data compatible with pulmonary tuberculosis. (author)

  14. Screening of Kenyan medicinal plants for antimalarial effects on Plasmodium falciparum in vitror. Final report for the period 15 December 1993 - 31 December 1994

    International Nuclear Information System (INIS)

    The antimalarial activities of extracts of Albizia gummifera and Aspilia mossambicensis against culture adapted isolates of Plasmodium falciparum were evaluated using an in citro 3H-hypoxanthine uptake technique. Chloroquine was used as a standard antimalarial drug for comparison with the plant extracts. The plant extracts showed various levels of activities (expressed as 50% inhibitory concentration (IC50s) in ug/ml of test culture) against P. falciparum in vitro, with Al gummifera showing the highest activity (eman IC50 of 5.98 ± 2.9 SD, n=6), followed by A. mossambicensis (mean IC50 73.36 ± 59.3 SD, n=18). The mean antimalarial activity of chloroquine (in ug/ml) was 0.037 (± 0.04 SD, n=10), far higher than that of the plant extracts. (author). 5 refs, 2 tabs

  15. Primary care patient willingness for genetic testing for salt-sensitive hypertension: a cross sectional study

    OpenAIRE

    Okayama, Masanobu; Takeshima, Taro; Ae, Ryusuke; Harada, Masanori; Kajii, Eiji

    2013-01-01

    Background The current research into single nucleotide polymorphisms has extended the role of genetic testing to the identification of increased risk for common medical conditions. Advances in genetic research may soon necessitate preparation for the role of genetic testing in primary care medicine. This study attempts to determine what proportion of patients would be willing to undergo genetic testing for salt-sensitive hypertension in a primary care setting, and what factors are related to ...

  16. Testing Visual Sensitivity to the Speed and Direction of Motion in Lizards

    OpenAIRE

    Woo, Kevin L.

    2006-01-01

    Testing visual sensitivity in any species provides basic information regarding behaviour, evolution, and ecology. However, testing specific features of the visual system provide more empirical evidence for functional applications. Investigation into the sensory system provides information about the sensory capacity, learning and memory ability, and establishes known baseline behaviour in which to gauge deviations (Burghardt, 1977). However, unlike mammalian or avian systems, testing for learn...

  17. Sensitivity of laboratory tests of gravitation beyond the geometrical optics limit

    International Nuclear Information System (INIS)

    A report is given of a laboratory experiment that reached the sensitivity attained so far in extraterrestrial tests of gravitation beyond the limit of geometrical optics. The sensitivity achieved here in searching for a hypothetical relative change in the velocity of light (deltac/c -12) seems, however, already near to the presumable maximum for experiments carried out on the earth's surface with static fields. (Auth.)

  18. Increased retest reactivity by both patch and use test with methyldibromoglutaronitrile in sensitized individuals

    DEFF Research Database (Denmark)

    Jensen, Charlotte D; Johansen, Jeanne Duus; Menné, Torkil;

    2006-01-01

    -exposure by both a patch test challenge and a use test with a liquid soap preserved with MDBGN. MDBGN dermatitis was elicited on the back and arms of sensitized individuals. One month later the previously eczematous areas were challenged with MDBGN. On the back, the test sites were patch-tested with a serial...... dilution of MDBGN and a use test was performed on the arms with an MDBGN-containing soap. A statistically significant increased response was seen on the areas with previous dermatitis on the back. Eight of the nine patients who developed dermatitis on the arms from the MDBGN-containing soap had an...

  19. Suppression of reduced sensitivity of eddy current testing depending on defect orientation

    International Nuclear Information System (INIS)

    Stress corrosion cracking (SCC) is generated on material structures in nuclear power plants. An eddy current testing (ECT) is used as a method for inspection techniques of a SCC. However when the eddy current direction is in parallel with defect direction, sensitivity of our ECT drops drown to one-quarter than a perpendicular direction. In order to prevent from this reduced sensitivity, Invert Exciting Method was developed. Adjacent exciter coils, which are located in two lines, are alternately opposite in phase of current. Therefore adjacent eddy currents, which are formed in the surface of metallic specimens, are also alternately opposite in phased of current. Then these eddy currents interfere with each other. Consequently eddy currents are inclined to scan direction. Using inclined eddy currents, the ECT has equal detection sensitivity for both defects parallel and perpendicular to scan direction. On the other hand, sensitivity drops down for defects in the same direction to inclined eddy currents. Then we added the function to inverse the phase for exciter coils in a set of line to the ECT system. Hereby the ECT can form symmetrical inclined eddy currents and prevent from reduced sensitivity. We applied Invert Exciting Method to the ECT system and conducted defect detection tests. As a result, we confirmed that detection sensitivity for both parallel and perpendicular defects are equal and Invert Exciting Method is effective in suppression of reduced sensitivity of the ECT depending on defect orientation. (author)

  20. Comparison of two different sensitivity testing agard for detecting methicillin resistance in staphylococcus aureus

    International Nuclear Information System (INIS)

    To compare the accuracy of Mueller-Hinton agar and Isosensitest agar using cefoxitin disc for detecting methicillin resistant Staphylococcus aureus using mecA gene PCR assay as gold standard. One hundred clinical isolates of Staphylococcus aureus were evaluated; 64 MRSA (methicillin resistant Staphylococcus aureus) and 36 MSSA (methicillin sensitive Staphylococcus aureus) by mecA PCR assay. All the isolates were tested with cefoxitin 30 macro g disc using semi-confluent growth on Mueller-Hinton agar as well as on Iso-sensitest agar in ambient air at 35-37degree C after an overnight incubation as per recommendations of Clinical and Laboratory Standard Institute. Following diameters provided the best sensitivity and specificity without substantial overlapping between the zones of resistant and sensitive isolates; Mueller-Hinton agar: R/sup 2/ 20 mm (sensitivity 100% and specificity 100%), S/sup 3/ 22 mm (sensitivity 97.2% and specificity 100%), and Iso-sensitest agar: R/sup 2/ 26 mm (sensitivity 100% and specificity100%), S/sup 3/ 26 mm (sensitivity 100% and specificity 100%). High accuracy was obtained with cefoxitin disc on both media. Performance of both media was equally convincing for reliable prediction of methicillin resistance in Staphylococcus aureus by placing cefoxitin 30 macro g disc on either of these in routine susceptibility testing. (author)

  1. Sensitivity analysis methods and a biosphere test case implemented in EIKOS

    International Nuclear Information System (INIS)

    Computer-based models can be used to approximate real life processes. These models are usually based on mathematical equations, which are dependent on several variables. The predictive capability of models is therefore limited by the uncertainty in the value of these. Sensitivity analysis is used to apportion the relative importance each uncertain input parameter has on the output variation. Sensitivity analysis is therefore an essential tool in simulation modelling and for performing risk assessments. Simple sensitivity analysis techniques based on fitting the output to a linear equation are often used, for example correlation or linear regression coefficients. These methods work well for linear models, but for non-linear models their sensitivity estimations are not accurate. Usually models of complex natural systems are non-linear. Within the scope of this work, various sensitivity analysis methods, which can cope with linear, non-linear, as well as non-monotone problems, have been implemented, in a software package, EIKOS, written in Matlab language. The following sensitivity analysis methods are supported by EIKOS: Pearson product moment correlation coefficient (CC), Spearman Rank Correlation Coefficient (RCC), Partial (Rank) Correlation Coefficients (PCC), Standardized (Rank) Regression Coefficients (SRC), Sobol' method, Jansen's alternative, Extended Fourier Amplitude Sensitivity Test (EFAST) as well as the classical FAST method and the Smirnov and the Cramer-von Mises tests. A graphical user interface has also been developed, from which the user easily can load or call the model and perform a sensitivity analysis as well as uncertainty analysis. The implemented sensitivity analysis methods has been benchmarked with well-known test functions and compared with other sensitivity analysis software, with successful results. An illustration of the applicability of EIKOS is added to the report. The test case used is a landscape model consisting of several linked

  2. Fighting fire with fire: mass antimalarial drug administrations in an era of antimalarial resistance.

    Science.gov (United States)

    von Seidlein, Lorenz; Dondorp, Arjen

    2015-06-01

    The emergence and spread of antimalarial resistance has been a major liability for malaria control. The spread of chloroquine-resistant Plasmodium falciparum strains had catastrophic consequences for people in malaria-endemic regions, particularly in sub-Saharan Africa. The recent emergence of artemisinin-resistant P. falciparum strains is of highest concern. Current efforts to contain artemisinin resistance have yet to show success. In the absence of more promising plans, it has been suggested to eliminate falciparum malaria from foci of artemisinin resistance using a multipronged approach, including mass drug administrations. The use of mass drug administrations is controversial as it increases drug pressure. Based on current knowledge it is difficult to conceptualize how targeted malaria elimination could contribute to artemisinin resistance, provided a full treatment course is ensured. PMID:25831482

  3. In vitro Potentiation of Antimalarial Activities by Daphnetin Derivatives Against Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    FANG HUANG; LIN-HUA TANG; LIN-QIAN YU; YI-CHANG NI; QIN-MEI WANG; FA-JUN NAN

    2006-01-01

    Objective To screen the antimalarial compounds of daphnetin derivatives against Plasmodium falciparum in vitro. Method Plasmodium faciparum (FCC1) was cultured in vitro by a modified method of Trager and Jensen. Antimalarial compounds were screened by microscopy-based assay and microfluorimetric method. Results DA79 and DA78 showed potent antimalarial activity against Plasmodium falciparum cultured in vitro. Conclusion Though the relationship between the structures of daphnetin derivatives and their antimalarial activities has not been clarified yet, this study may provide a new direction for discovery of more potential antimalarial compounds.

  4. Engineering Sensitivity Improvement of Helium Mass Spectrometer Leak Detection System by Means Global Hard Vacuum Test

    International Nuclear Information System (INIS)

    The engineering sensitivity improvement of Helium mass spectrometer leak detection using global hard vacuum test configuration has been done. The purpose of this work is to enhance the sensitivity of the current leak detection of pressurized method (sniffer method) with the sensitivity of 10-3 ∼ 10-5 std cm3/s, to the global hard vacuum test configuration method which can be achieved of up to 10-8 std cm3/s. The goal of this research and development is to obtain a Helium leak test configuration which is suitable and can be used as routine bases in the quality control tests of FPM capsule and AgInCd safety control rod products. The result is an additional instrumented vacuum tube connected with conventional Helium mass spectrometer. The pressure and temperature of the test object during the leak measurement are simulated by means of a 4.1 kW capacity heater and Helium injection to test object, respectively. The addition of auxiliary mechanical vacuum pump of 2.4 l/s pumping speed which is directly connected to the vacuum tube, will reduce 86 % of evacuation time. The reduction of the measured sensitivity due to the auxiliary mechanical vacuum pump can be overcome by shutting off the pump soon after Helium mass spectrometer reaches its operating pressure condition. (author)

  5. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname

    Directory of Open Access Journals (Sweden)

    Evans Lawrence

    2012-06-01

    Full Text Available Abstract Background Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector and unlicensed facilities (informal sector is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. Methods To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Results Quality issues were observed in 45 of 77 (58% anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30 and 11% (5/47 respectively. A higher proportion of medicines sampled from the private sector 34% (11/32 failed quality control tests versus 16% (7/45 in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86% were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. Conclusions The findings of the studies in both countries point to

  6. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    Science.gov (United States)

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  7. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    Directory of Open Access Journals (Sweden)

    Angeli Kodjo

    2016-01-01

    Full Text Available A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT, using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1 positive (n=50; (2 borderline (n=35; and (3 negative (n=50. Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted, respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  8. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    Science.gov (United States)

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  9. Screening Test for Detection of Leptinotarsa decemlineata (Say Sensitivity to Insecticides

    Directory of Open Access Journals (Sweden)

    Dušanka Inđić

    2012-01-01

    Full Text Available In 2009, the sensitivity of 15 field populations of Colorado potato beetle (Leptinotarsadecemlineata Say. - CPB was assessed to chlorpyrifos, cypermethrin, thiamethoxam and fipronil,four insecticides which are mostly used for its control in Serbia. Screening test that allows rapidassessment of sensitivity of overwintered adults to insecticides was performed. Insecticideswere applied at label rates, and two, five and 10 fold higher rates by soaking method (5 sec.Mortality was assessed after 72h. From 15 monitored populations of CPB, two were sensitiveto label rate of chlorpyrifos, one was slightly resistant, 11 were resistant and one populationwas highly resistant. Concerning cypermethrin, two populations were sensitive, two slightlyresistant, five were resistant and six highly resistant. Highly sensitive to thiamethoxam labelrate were 12 populations, while three were sensitive. In the case of fipronil applied at label rate,two populations were highly sensitive, six sensitive, one slightly resistant and six were resistant.The application of insecticides at higher rates (2, 5 and 10 fold, that is justified only in bioassays,provided a rapid insight into sensitivity of field populations of CPB to insecticides.

  10. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  11. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    Directory of Open Access Journals (Sweden)

    Scott R Fry

    2011-06-01

    Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

  12. Use of genotoxicity information in the development of integrated testing strategies (ITS) for skin sensitization.

    Science.gov (United States)

    Mekenyan, Ovanes; Patlewicz, Grace; Dimitrova, Gergana; Kuseva, Chanita; Todorov, Milen; Stoeva, Stoyanka; Kotov, Stefan; Donner, E Maria

    2010-10-18

    Skin sensitization is an end point of concern for various legislation in the EU, including the seventh Amendment to the Cosmetics Directive and Registration Evaluation, Authorisation and Restriction of Chemicals (REACH). Since animal testing is a last resort for REACH or banned (from 2013 onward) for the Cosmetics Directive, the use of intelligent/integrated testing strategies (ITS) as an efficient means of gathering necessary information from alternative sources (e.g., in vitro, (Q)SARs, etc.) is gaining widespread interest. Previous studies have explored correlations between mutagenicity data and skin sensitization data as a means of exploiting information from surrogate end points. The work here compares the underlying chemical mechanisms for mutagenicity and skin sensitization in an effort to evaluate the role mutagenicity information can play as a predictor of skin sensitization potential. The Tissue Metabolism Simulator (TIMES) hybrid expert system was used to compare chemical mechanisms of both end points since it houses a comprehensive set of established structure-activity relationships for both skin sensitization and mutagenicity. The evaluation demonstrated that there is a great deal of overlap between skin sensitization and mutagenicity structural alerts and their underlying chemical mechanisms. The similarities and differences in chemical mechanisms are discussed in light of available experimental data. A number of new alerts for mutagenicity were also postulated for inclusion into TIMES. The results presented show that mutagenicity information can provide useful insights on skin sensitization potential as part of an ITS and should be considered prior to any in vivo skin sensitization testing being initiated. PMID:20845941

  13. Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

    Directory of Open Access Journals (Sweden)

    A.M. Valença

    2002-07-01

    Full Text Available The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2 challenge test of panic disorder (PD patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1 35% CO2 and 65% O2, and 2 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7% respiratory PD subtype patients and 5 of 11 (43.4% nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test. Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

  14. Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection.

    Science.gov (United States)

    Arruda, Mauro Maciel de; Figueiredo, Fabiano Borges; Marcelino, Andreza Pain; Barbosa, José Ronaldo; Werneck, Guilherme Loureiro; Noronha, Elza Ferreira; Romero, Gustavo Adolfo Sierra

    2016-03-01

    In Brazil, human and canine visceral leishmaniasis (CVL) caused by Leishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescence assays (IFA) as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA), decreased sensitivity (83.3%) and increased specificity (92.5%) were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL. PMID:26910354

  15. Sensitivity and specificity of parallel or serial serological testing for detection of canine Leishmania infection

    Directory of Open Access Journals (Sweden)

    Mauro Maciel de Arruda

    2016-01-01

    Full Text Available In Brazil, human and canine visceral leishmaniasis (CVL caused byLeishmania infantum has undergone urbanisation since 1980, constituting a public health problem, and serological tests are tools of choice for identifying infected dogs. Until recently, the Brazilian zoonoses control program recommended enzyme-linked immunosorbent assays (ELISA and indirect immunofluorescence assays (IFA as the screening and confirmatory methods, respectively, for the detection of canine infection. The purpose of this study was to estimate the accuracy of ELISA and IFA in parallel or serial combinations. The reference standard comprised the results of direct visualisation of parasites in histological sections, immunohistochemical test, or isolation of the parasite in culture. Samples from 98 cases and 1,327 noncases were included. Individually, both tests presented sensitivity of 91.8% and 90.8%, and specificity of 83.4 and 53.4%, for the ELISA and IFA, respectively. When tests were used in parallel combination, sensitivity attained 99.2%, while specificity dropped to 44.8%. When used in serial combination (ELISA followed by IFA, decreased sensitivity (83.3% and increased specificity (92.5% were observed. Serial testing approach improved specificity with moderate loss in sensitivity. This strategy could partially fulfill the needs of public health and dog owners for a more accurate diagnosis of CVL.

  16. In vitro study of drug sensitivity of Plasmodium falciparum: assessment of semi-microtest by /sup 3/H-hypoxanthine incorporation

    Energy Technology Data Exchange (ETDEWEB)

    Le Bras, J.; Andrieu, B.; Hatin, I.; Savel, J.; Coulaud, J.P. (Hopital Claude-Bernard, 75 - Paris (France))

    1984-05-01

    Recent advances in cultivation methods and knowledge of in vitro response of Plasmodium falciparum to antimalarials have led to improved chemosensitivity tests. The semi-microtest is a useful tool for screening presumptive antimalarials, and also for the testing sensitivity of strains recovered from patients in hospital and field studies to currently used drugs. Microscopic parasite counts on thin blood films can be replaced by measurement of /sup 3/H-hypoxanthine by the uptake parasite. Conditions which ensure optimal parasite growth and high radioisotope incorporation are described. Wells containing less than 3.10/sup 4/ asexualparasites can be studied with this method. Results of the semi-microtest are closely correlated with those of microscopic parasite count. Advantages of both methods are discussed.

  17. A dataset on 145 chemicals tested in alternative assays for skin sensitization undergoing prevalidation.

    Science.gov (United States)

    Natsch, Andreas; Ryan, Cindy A; Foertsch, Leslie; Emter, Roger; Jaworska, Joanna; Gerberick, Frank; Kern, Petra

    2013-11-01

    Skin sensitization is a key endpoint for cosmetic ingredients, with a forthcoming ban for animal testing in Europe. Four alternative tests have so far been submitted to ECVAM prevalidation: (i) MUSST and (ii) h-Clat assess surface markers on dendritic cell lines, (iii) the direct peptide reactivity assay (DPRA) measures reactivity with model peptides and (iv) the KeratinoSens(TM) assay which is based on detection of Nrf2-induced luciferase. It is anticipated that only an integrated testing strategy (ITS) based on a battery of tests might give a full replacement providing also a sensitization potency assessment, but this concept should be tested with a data-driven analysis. Here we report a database on 145 chemicals reporting the quantitative endpoints measured in a U937- test, the DPRA and KeratinoSens(TM) . It can serve to develop data-driven ITS approaches as we show in a parallel paper and provides a view as to the current ability to predict with in vitro tests as we are entering 2013. It may also serve as reference database when benchmarking new molecules with in vitro based read-across and find use as a reference database when evaluating new tests. The tests and combinations thereof were evaluated for predictivity, and overall a similar predictivity was found as before on three-fold smaller datasets. Analysis of the dose-response parameters of the individual tests indicates a correlation to sensitization potency. Detailed analysis of chemicals false-negative and false-positive in two tests helped to define limitations in the tests but also in the database derived from animal studies. PMID:23576290

  18. Gas chromatographic method for the determination of lumefantrine in antimalarial finished pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Sultan Suleman

    2015-09-01

    Full Text Available A simple method has been developed and validated for quantitative determination of lumefantrine in antimalarial finished pharmaceutical products using gas chromatography coupled to flame ionization detector. Lumefantrine was silylated with N,O–bis(trimethyl-silyltrifluoro-acetamide at 70°C for 30 minutes, and chromatographic separation was conducted on a fused silica capillary (HP-5, 30 m length × 0.32 mm i.d., 0.25 μm film thickness column. Evaluation of the method within analytical quality-by-design principles, including a central composite face-centered design for the sample derivatization process and Plackett–Burman robustness verification of the chromatographic conditions, indicated that the method has acceptable specificity toward excipients and degradants, accuracy [mean recovery = 99.5%, relative standard deviation (RSD = 1.0%], linearity (=0.9986, precision (intraday = 96.1% of the label claim, RSD = 0.9%; interday = 96.3% label claim, RSD = 0.9%, and high sensitivity with detection limits of 0.01 μg/mL. The developed method was successfully applied to analyze the lumefantrine content of marketed fixed-dose combination antimalarial finished pharmaceutical products.

  19. Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor.

    Science.gov (United States)

    Goldgof, Gregory M; Durrant, Jacob D; Ottilie, Sabine; Vigil, Edgar; Allen, Kenneth E; Gunawan, Felicia; Kostylev, Maxim; Henderson, Kiersten A; Yang, Jennifer; Schenken, Jake; LaMonte, Gregory M; Manary, Micah J; Murao, Ayako; Nachon, Marie; Stanhope, Rebecca; Prescott, Maximo; McNamara, Case W; Slayman, Carolyn W; Amaro, Rommie E; Suzuki, Yo; Winzeler, Elizabeth A

    2016-01-01

    The spiroindolones, a new class of antimalarial medicines discovered in a cellular screen, are rendered less active by mutations in a parasite P-type ATPase, PfATP4. We show here that S. cerevisiae also acquires mutations in a gene encoding a P-type ATPase (ScPMA1) after exposure to spiroindolones and that these mutations are sufficient for resistance. KAE609 resistance mutations in ScPMA1 do not confer resistance to unrelated antimicrobials, but do confer cross sensitivity to the alkyl-lysophospholipid edelfosine, which is known to displace ScPma1p from the plasma membrane. Using an in vitro cell-free assay, we demonstrate that KAE609 directly inhibits ScPma1p ATPase activity. KAE609 also increases cytoplasmic hydrogen ion concentrations in yeast cells. Computer docking into a ScPma1p homology model identifies a binding mode that supports genetic resistance determinants and in vitro experimental structure-activity relationships in both P. falciparum and S. cerevisiae. This model also suggests a shared binding site with the dihydroisoquinolones antimalarials. Our data support a model in which KAE609 exerts its antimalarial activity by directly interfering with P-type ATPase activity. PMID:27291296

  20. The antimalarial drug quinine interferes with serotonin biosynthesis and action

    DEFF Research Database (Denmark)

    Islahudin, Farida; Tindall, Sarah M.; Mellor, Ian R.;

    2014-01-01

    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmit...

  1. Role of sensitive test-cultures in manifestation of antagonism by human symbiotic bacteria

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    Semenov А.V.

    2011-06-01

    Full Text Available Aim. The study considers the influence of sensitive test-cultures on antagonistic activity and production antimicrobial factors by indigenous and probiotic microorganisms. Material. The original method has been used. It is based on determination of survival of sensitive test-culture under the action of cultural liquids of antagonist processed by metabolites and peptidoglycan of sensitive culture. Resalts. The important role of sensitive test-culture in manifestation of the antagonism active microorganisms has been proved. Received data have proved that antagonistic bacterial activity is a result of cross-species interaction between active and sensitive cultures. The effectors are antimicrobial factors and their regulators. The ability of bacterial peptidoglycan to regulate the cross-species interaction between prokaryotes has been firstly shown. Conclusion. The article concludes that the investigation has revealed new mechanisms of colonization resistance of biotope. It has opened prospects of development of principal new probiotic, prebiotic, sinbiotic, biologically active additive and functional products on the basis of microbial stimulators of bacterial antagonism

  2. Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence "transmission blocking" assay.

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    Joël Lelièvre

    Full Text Available BACKGROUND: Current anti-malarial drugs have been selected on the basis of their activity against the symptom-causing asexual blood stage of the parasite. Which of these drugs also target gametocytes, in the sexual stage responsible for disease transmission, remains unknown. Blocking transmission is one of the main strategies in the eradication agenda and requires the identification of new molecules that are active against gametocytes. However, to date, the main limitation for measuring the effect of molecules against mature gametocytes on a large scale is the lack of a standardized and reliable method. Here we provide an efficient method to produce and purify mature gametocytes in vitro. Based on this new procedure, we developed a robust, affordable, and sensitive ATP bioluminescence-based assay. We then assessed the activity of 17 gold-standard anti-malarial drugs on Plasmodium late stage gametocytes. METHODS AND FINDINGS: Difficulties in producing large amounts of gametocytes have limited progress in the development of malaria transmission blocking assays. We improved the method established by Ifediba and Vanderberg to obtain viable, mature gametocytes en masse, whatever the strain used. We designed an assay to determine the activity of antimalarial drugs based on the intracellular ATP content of purified stage IV-V gametocytes after 48 h of drug exposure in 96/384-well microplates. Measurements of drug activity on asexual stages and cytotoxicity on HepG2 cells were also obtained to estimate the specificity of the active drugs. CONCLUSIONS: The work described here represents another significant step towards determination of the activity of new molecules on mature gametocytes of any strain with an automated assay suitable for medium/high-throughput screening. Considering that the biology of the forms involved in the sexual and asexual stages is very different, a screen of our 2 million-compound library may allow us to discover novel anti-malarial

  3. Comparison of three land-surface schemes with the Fourier amplitude sensitivity test (FAST)

    OpenAIRE

    Rodríguez-Camino, Ernesto; Avissar, Roni

    2011-01-01

    This paper explores which are the land-surface parameters playing a key rôle in three surfaceschemes, namely the land-atmosphere interactive dynamics (LAID), the interaction soil-biosphere-atmosphere (ISBA) and the biosphere-atmosphere transfer scheme (BATS). The Fourieramplitude sensitivity test (FAST) was used for that purpose. This test estimates the relativecontribution of model input parameters to the variance of surface heat fluxes. This analysisdemonstrates that, for the three consider...

  4. A simple nomogram for sample size for estimating sensitivity and specificity of medical tests

    OpenAIRE

    Malhotra Rajeev; Indrayan A

    2010-01-01

    Sensitivity and specificity measure inherent validity of a diagnostic test against a gold standard. Researchers develop new diagnostic methods to reduce the cost, risk, invasiveness, and time. Adequate sample size is a must to precisely estimate the validity of a diagnostic test. In practice, researchers generally decide about the sample size arbitrarily either at their convenience, or from the previous literature. We have devised a simple nomogram that yields statistically valid sample size ...

  5. Evaluation of the sensitivity of freshwater organisms used in toxicity tests of wastewater from explosives company.

    Science.gov (United States)

    Ribeiro, Elaine Nolasco; da Silva, Flávio Teixeira; de Paiva, Teresa Cristina Brazil

    2012-10-01

    Explosives industries are a source of toxic discharge. The aim of this study was to compare organisms sensitivity (Daphnia similis, Danio rerio, Escherichia coli and Pseudomonas putida) in detecting acute toxicity in wastewater from two explosives, 2,4,6-TNT (TNT) and nitrocellulose. The samples were collected from an explosives company in the Paraiba Valley, São Paulo, Brazil. The effluents from TNT and nitrocellulose production were very toxic for tested organisms. Statistical tests indicated that D. similis and D. rerio were the most sensitive organisms for toxicity detection in effluents from 2,4,6-TNT and nitrocellulose production. The P. putida bacteria was the organism considered the least sensitive in indicating toxicity in effluents from nitrocellulose. PMID:22872378

  6. Andrographolide: A Novel Antimalarial Diterpene Lactone Compound from Andrographis paniculata and Its Interaction with Curcumin and Artesunate

    Directory of Open Access Journals (Sweden)

    Kirti Mishra

    2011-01-01

    Full Text Available Andrographolide (AND, the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS, andrographolide (AND, and curcumin (CUR were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND was found synergistic with curcumin (CUR and addictively interactive with artesunate (AS. In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%, compared to the control (81%, but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

  7. Comparative sensitivity of the cnidarian Exaiptasia pallida and a standard toxicity test suite: testing whole effluents intended for ocean disposal.

    Science.gov (United States)

    Howe, P L; Reichelt-Brushett, A J; Krassoi, R; Micevska, T

    2015-09-01

    The sea anemone Exaiptasia pallida (formally Aiptasia pulchella) has been identified as a valuable test species for tropical marine ecotoxicology. Here, the sensitivities of newly developed endpoints for E. pallida to two unidentified whole effluents were compared to a standard suite of temperate toxicity test species and endpoints that are commonly used in toxicological risk assessments for tropical marine environments. For whole effluent 1 (WE1), a 96-h lethal concentration 50 % (LC50) of 40 (95 % confidence intervals, 30-54) % v/v and a 12-day LC50 of 12 (9-15) % v/v were estimated for E. pallida, exhibiting a significantly higher sensitivity than standard sub-lethal endpoints in Allorchestes compressa (96-h effective concentration 50 % (EC50) of >100 % v/v for immobilisation) and Hormosira banksii (72-h EC50 of >100 % v/v for germination), and a similar sensitivity to Mytilus edulis galloprovincialis larval development with a 48-h LC50 of 29 (28-30) % v/v. Sub-lethal effects of whole effluent 2 (WE2) on E. pallida pedal lacerate development resulted in an 8-day EC50 of 7 (3-11) % v/v, demonstrating comparable sensitivity of this endpoint to standardised sub-lethal endpoints in H. banksii (72-h EC50 of 11 (10-11) % v/v for germination), M. edulis galloprovincialis (48-h EC50 for larval development of 12 (9-14) % v/v) and Heliocidaris tuberculata (1-h EC50 of 13 (12-14) % v/v for fertilisation; 72-h EC50 of 26 (25-27) % v/v for larval development) and a significantly higher sensitivity than A. compressa immobilisation (96-h EC50 of >100 % v/v). The sensitivity of E. pallida compared to a standard test species suite highlights the value in standardising the newly developed toxicity test methods for inclusion in routine toxicological risk assessment of complex whole effluents. Importantly, this species provides an additional taxonomic group to the test species that are currently available for tropical marine ecotoxicology and

  8. History and sensitivity comparison of the Spirodela polyrhiza microbiotest and Lemna toxicity tests

    Directory of Open Access Journals (Sweden)

    Baudo R.

    2015-01-01

    Full Text Available The history of toxicity tests with duckweeds shows that these assays with free-floating aquatic angiosperms are gaining increasing attention in ecotoxicological research and applications. Standard tests have been published by national and international organizations, mainly with the test species Lemna minor and Lemna gibba. Besides the former two test species the great duckweed Spirodela polyrhiza is to date also regularly used in duckweed testing. Under unfavorable environmental conditions, the latter species produces dormant stages (turions and this has triggered the attention of two research groups from Belgium and Greece to jointly develop a “stock culture independent” microbiotest with S. polyrhiza. A 72 h new test has been worked out which besides its independence of stock culturing and maintenance of live stocks is very simple and practical to perform, and much less demanding in space and time than the conventional duckweed tests. Extensive International Interlaboratory Comparisons on the S. polyrhiza microbiotest showed its robustness and reliability and triggered the decision to propose this new assay to the ISO for endorsement and publication as a standard toxicity test for duckweeds. Sensitivity comparison of the 72 h S. polyrhiza microbiotest with the 7d L. minor assay for 22 compounds belonging to different groups of chemicals revealed that based on growth as the effect criterion both duckweed assays have a similar sensitivity. Taking into account its multiple advantages and assets, the S. polyrhiza microbiotest is a reliable and attractive alternative to the conventional duckweed tests.

  9. Synthesis, Cytotoxic and Antimalarial Activities of Benzoyl Thiosemicarbazone Analogs of Isoquinoline and Related Compounds

    Directory of Open Access Journals (Sweden)

    Somsak Ruchirawat

    2010-02-01

    Full Text Available Thiosemicarbazone analogs of papaveraldine and related compounds 1–6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1–5 displayed cytotoxicity toward all the tested cell lines, while compounds 2–5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 µg/mL, respectively. In addition, 2-benzoylpyridine thio-semicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development.

  10. Evaluation of the Quality of Artemisinin-Based Antimalarial Medicines Distributed in Ghana and Togo

    Directory of Open Access Journals (Sweden)

    Dorcas Osei-Safo

    2014-01-01

    Full Text Available This study, conducted as part of our overall goal of regular pharmacovigilance of antimalarial medicines, reports on the quality of 132 artemisinin-based antimalarial medicines distributed in Ghana and Togo. Three methods were employed in the quality evaluation—basic (colorimetric tests for establishing the identity of the requisite active pharmaceutical ingredients (APIs, semi-quantitative TLC assay for the identification and estimation of API content, and HPLC assay for a more accurate quantification of API content. From the basic tests, only one sample totally lacked API. The HPLC assay, however, showed that 83.7% of the ACTs and 57.9% of the artemisinin-based monotherapies failed to comply with international pharmacopoeia requirements due to insufficient API content. In most of the ACTs, the artemisinin component was usually the insufficient API. Generally, there was a good correlation between the HPLC and SQ-TLC assays. The overall failure rates for both locally manufactured (77.3% and imported medicines (77.5% were comparable. Similarly the unregistered medicines recorded a slightly higher overall failure rate (84.7% than registered medicines (70.8%. Only two instances of possible cross-border exchange of medicines were observed and there was little difference between the medicine quality of collections from border towns and those from inland parts of both countries.

  11. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol

    International Nuclear Information System (INIS)

    Graphical abstract: A multianalyte immunochromatographic test strip was developed for the rapid detection of two β2-agonists. Due to the application of chemiluminescent detection, this quantitative method shows much higher sensitivity. - Highlights: • An immunochromatographic test strip was developed for detection of multiple β2-agonists. • The whole assay process can be completed within 20 min. • The proposed method shows much higher sensitivity due to the application of CL detection. • It is a portable analytical tool suitable for field analysis and rapid screening. - Abstract: A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β2-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β2-agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50–40 and 0.10–50 ng mL−1, with the detection limits of 0.20 and 0.040 ng mL−1 (S/N = 3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β2-agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety

  12. Sensitivity of screening-level toxicity tests using soils from a former petroleum refinery

    International Nuclear Information System (INIS)

    The authors tested five composite soil samples from a former refinery. The samples included a reference soil (Mineral Oil and Grease, MO and G < 40 ppm), thermally-treated soil, biotreated soil, and two untreated soils. They evaluated toxicity using the earthworm E. foetida, lettuce, cress, barley, Microtox, green algae, fathead minnow, and D. magna. The endpoints measured were lethality, seed germination, root elongation, growth, and bioluminescence. Toxicity, as measured by the number of positive responses, increased as follows: biotreated soil < untreated soil No. 1 < reference soil < thermally-treated soil and untreated soil No. 2. The biotreated soil generated only one positive response, whereas the thermally-treated soil and untreated soil No. 2 generated five positive responses. The most sensitive and discriminant terrestrial endpoint was lettuce root elongation which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was barley seed germination for which no toxicity was detected. The most sensitive and discriminant aquatic endpoint was green algae growth which responded to untreated soil No. 1, thermally-treated soil, and reference soil. The least sensitive was D. magna for which no toxicity was detected. Overall, soil and aqueous extract toxicity was spotty and no consistent patterns emerged to differentiate the five soils. Biotreatment significantly reduced the effects of the contamination. Aqueous toxicity was measured in the reference soil, probably because of the presence of unknown dissolved compounds in the aqueous extract. Finally, clear differences in sensitivity existed among the test species

  13. The sensitizing potential of metalworking fluid biocides (phenolic and thiazole compounds) in the guinea-pig maximization test in relation to patch-test reactivity in eczema patients

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hamann, K

    1984-01-01

    containing 1,2-benzisothiazolin-3-one were weak sensitizers, while Preventol CMK and Preventol L, both containing chlorocresol, were classified as extreme potential sensitizers. Both the weak and the extreme experimental sensitizers are occasional human sensitizers. The interpretation of the test results is......The sensitizing potential of seven industrial antimicrobial agents was evaluated using the guinea-pig maximization test. Preventol O extra (o-phenylphenol) did not produce a sensitization reaction. Preventol ON extra (sodium salt of o-phenylphenol), Preventol GD (dichlorophene) and Proxel XL and HL...

  14. Four nondestructive electrochemical tests for detecting sensitization in type 304 and 304L stainless steels

    International Nuclear Information System (INIS)

    Three different electrochemical reactivation tests are compared with etch structures produced in the electrolytic oxalic acid etch test. These nondestructive tests are needed to evaluate welded stainless steel pipes and other plant equipment for susceptibility to intergranular attack. Sensitization associated with precipitates of chromium carbides at grain boundaries can make these materials subject to intergranular attack in acids and, in particular, to intergranular stress corrosion cracking in high-temperature (2890C) water on boiling water nuclear reactor power plants. In the first of the two older reactivation tests, sensitization is detected by the electrical charge generated during reactivation. In the second, it is measured by the ratio of maximum currents generated by a prior anodic loop and the reactivation loop. A third, simpler reactivation method based on a measurement of the maximum current generated during reactivation is proposed. If the objective of the field tests, which are to be carried out with portable equipment, is to distinguish between nonsensitized and sensitized material, this can be accomplished most simply, most rapidly, and at lowest cost by an evaluation of oxalic acid etch structures

  15. A simple nomogram for sample size for estimating sensitivity and specificity of medical tests

    Directory of Open Access Journals (Sweden)

    Malhotra Rajeev

    2010-01-01

    Full Text Available Sensitivity and specificity measure inherent validity of a diagnostic test against a gold standard. Researchers develop new diagnostic methods to reduce the cost, risk, invasiveness, and time. Adequate sample size is a must to precisely estimate the validity of a diagnostic test. In practice, researchers generally decide about the sample size arbitrarily either at their convenience, or from the previous literature. We have devised a simple nomogram that yields statistically valid sample size for anticipated sensitivity or anticipated specificity. MS Excel version 2007 was used to derive the values required to plot the nomogram using varying absolute precision, known prevalence of disease, and 95% confidence level using the formula already available in the literature. The nomogram plot was obtained by suitably arranging the lines and distances to conform to this formula. This nomogram could be easily used to determine the sample size for estimating the sensitivity or specificity of a diagnostic test with required precision and 95% confidence level. Sample size at 90% and 99% confidence level, respectively, can also be obtained by just multiplying 0.70 and 1.75 with the number obtained for the 95% confidence level. A nomogram instantly provides the required number of subjects by just moving the ruler and can be repeatedly used without redoing the calculations. This can also be applied for reverse calculations. This nomogram is not applicable for testing of the hypothesis set-up and is applicable only when both diagnostic test and gold standard results have a dichotomous category.

  16. ESTIMATION OF HIGHLY SENSITIVE TROPONIN TESTS IN THE DIAGNOSIS OF ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    L. V. Kremneva

    2016-05-01

    Full Text Available Review is devoted to the value of the use of highly sensitive troponin (hs-cTn tests in the diagnosis of acute coronary syndrome. The classification of the Tn-tests depending on their sensitivity is presented. The possible reasons of troponins appearance in blood of healthy people are shown. Authors consider a 3-hour algorithm for myocardial infarction (MI diagnostic, recommended by the expert group in 2012. Study results of 2011-2015 years are presented as the basis for the development of a one-hour MI diagnostic algorithm, recommended by the European Society of Cardiology in 2015. Authors discuss the results of studies showing that modern HS-cTnt tests (together with ECG assessment are capable to diagnose MI in the early stages. They significantly increase the number of identified MI, especially MI without ST segment elevation, as well as identify the group of patients with subsequent favorable prognosis.

  17. Noise sensitivity and diminished health: Testing moderators and mediators of the relationship

    Directory of Open Access Journals (Sweden)

    Erin M Hill

    2014-01-01

    Full Text Available The concept of noise sensitivity emerged in public health and psychoacoustic research to help explain individual differences in reactions to noise. Noise sensitivity has been associated with health problems, but the mechanisms underlying this relationship have yet to be fully examined. Participants (n = 1102 were residents of Auckland, New Zealand, who completed questionnaires and returned them through the post. Models of noise sensitivity and health were tested in the analyses using bootstrapping methods to examine indirect effects. Results indicated that gender and noise exposure were not significant moderators in the model. Perceived stress and sleep problems were significant mediators of the relationship between noise sensitivity and subjective health complaints, even after controlling for the influence of neuroticism. However, the relationship between noise sensitivity and mental health complaints (anxiety and depression was accounted for by the variance explained by neuroticism. Overall, this study provides considerable understanding of the relationship between noise sensitivity and health problems and identifies areas for further research in the field.

  18. SENSITIVITY AND VALIDITY OF A FUNCTIONAL TEST FOR AGILITY PERFORMANCE IN WATER POLO PLAYERS

    OpenAIRE

    Tucher, Guilherme; A. de S. Castro, Flávio; J.R.M. da Silva, António; D. Garrido, Nuno

    2016-01-01

    The aim of this study was to evaluate the sensitivity and validity of the Functional Test for Agility Performance (FTAP) in water polo players. Six elite junior (aged 16.33±0.82 years) male players and 65 competitive men (aged 18.1±4.3 years) who were classified in three groups (G1-3), participated in different phases of the test. The scores accomplished in FTAP at two periods (initial and final) were compared. They were correlated with the scores in Sprint/Agility Test and differences bet...

  19. Examination of sensitivity and specificity of some serological tests in diagnostics of bovine brucellosis

    Directory of Open Access Journals (Sweden)

    Matović Kazimir

    2008-01-01

    Full Text Available The most reliable diagnosis of an infectuous disease is confirmed by isolation of its pathogen. When it comes to brucellosis, it is important to know that brucella isolation is rarely successful; it is not only very complicated but is as well hazardous for laboratory workers. Due to the above mentioned reasons, it is reasonable to use serological tests for routine diagnosis of this zoonose. This paper deals with examination of bovine sera samples with the aim to detect the titer of specific antibodies against brucellosis. In order to choose and evaluate properly the best test in terms of applicability, speed of performance, and provision of correct results, five serological tests were assayed: rapid serum plate agglutination (Rose Bengal test, Brucella abortus bovis test (RB, BAB test; serum agglutination test (titration - by Wright, as micro method (mSAT; reaction of complement fixation, and also as micro method (mCF; indirect imunoenzyime test (iELISA and competitive imunoenzyme test (cELISA. This paper includes 630 samples of bovine blood sera, as well as positive and negative international antibrucella serum as the mandatory control. The presence of specific antibodies against brucella was determined in 125 samples of bovine blood sera. Based on the analysis of the results obtained, evaluation of sensitivity and specificity of these tests was conducted. iELISA and RB test proved to be the most sensitive, while the highest specificity was determined in mCF, and less specific were mSAT and iELISA. RB test had the lowest specificity.

  20. New microbioassays based on biomarkers are more sensitive to fluvial water micropollution than standard testing methods.

    Science.gov (United States)

    Esteban, S; Fernández Rodríguez, J; Díaz López, G; Nuñez, M; Valcárcel, Y; Catalá, M

    2013-07-01

    Recent investigations suggest that, despite lack of lethality in validated bioassays, micropollutants in surface waters could induce sublethal toxicity in sensitive taxa, jeopardizing their biological performance and eventually leading to populations' extinction. A broader array of testing species, the miniaturization of bioassays and the development of reliable biomarkers of damage are sought in order to improve ecological relevance and cost efficiency of environmental monitoring. Our aim is to assess the different sensitivity of validated bioassays and new approaches using biomarkers as sensitive endpoints of toxicity in spores of Polystichum setiferum and Danio rerio embryos. Six water samples were collected in Tagus basin in summer and winter. Samples tested induce no acute toxicity in validated methods (algae growth inhibition and daphnia mobility inhibition). Summer water samples induced acute membrane damage (lipid peroxidation) in Danio rerio embryos and hormetic increases in fern spore mitochondrial activity. One of the samples dramatically reduced mitochondrial activity indicating severe acute sublethal phytotoxicity. All the winter samples induced significant decreases in fern spore mitochondrial activity and membrane damage increases in Danio rerio embryo. Furthermore, three samples induced lethal phytotoxicity in fern spores. We conclude that the new microbioassays show a better sensitivity to fluvial water micropollution and confirm the necessity to test critical life stages such as development and provide cost-efficient methods for environmental monitoring. PMID:23618774

  1. Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and investigation of the presumed underlying mechanism of action

    Directory of Open Access Journals (Sweden)

    Mullié Catherine

    2012-03-01

    Full Text Available Abstract Background A better anti-malarial efficiency and lower neurotoxicity have been reported for mefloquine (MQ (+- enantiomer. However, the importance of stereoselectivity remains poorly understood as the anti-malarial activity of pure enantiomer MQ analogues has never been described. Building on these observations, a series of enantiopure 4-aminoalcohol quinoline derivatives has previously been synthesized to optimize the efficiency and reduce possible adverse effects. Their in vitro activity on Plasmodium falciparum W2 and 3D7 strains is reported here along with their inhibition of β-haematin formation and peroxidative degradation of haemin, two possible mechanisms of action of anti-malarial drugs. Results The (S-enantiomers of this series of 4-aminoalcohol quinoline derivatives were found to be at least as effective as both chloroquine (CQ and MQ. The derivative with a 5-carbon side-chain length was the more efficient on both P. falciparum strains. (R -enantiomers displayed an activity decreased by 2 to 15-fold as compared to their (S counterparts. The inhibition of β-haematin formation was significantly stronger with all tested compounds than with MQ, irrespective of the stereochemistry. Similarly, the inhibition of haemin peroxidation was significantly higher for both (S and (R-enantiomers of derivatives with a side-chain length of five or six carbons than for MQ and CQ. Conclusions The prominence of stereochemistry in the anti-malarial activity of 4-aminoalcohol quinoline derivatives is confirmed. The inhibition of β-haematin formation and haemin peroxidation can be put forward as presumed mechanisms of action but do not account for the stereoselectivity of action witnessed in vitro.

  2. Investigation of Indolglyoxamide and Indolacetamide Analogues of Polyamines as Antimalarial and Antitrypanosomal Agents

    Directory of Open Access Journals (Sweden)

    Jiayi Wang

    2014-05-01

    Full Text Available Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3 to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 μM, respectively and Plasmodium falciparum (K1 dual drug resistant strain (IC50 41 and 15 μM, respectively, but lacking in selectivity (L6 rat myoblast, IC50 24 μM and 25 μM, respectively. To expand the structure–activity relationship of this compound class towards both parasites, we have prepared and biologically tested a library of analogues that includes indoleglyoxyl and indoleacetic “capping acids”, and polyamines including spermine (PA3-4-3 and extended analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were typically found to exhibit the most potent antimalarial activity (IC50 10–92 nM but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6-methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T. brucei (IC50 0.18 μM identified in the study: it, however, also exhibited poor selectivity (L6 IC50 6.0 μM. There was no apparent correlation between antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9% reduction in parasitaemia.

  3. Basigin is a druggable target for host-oriented antimalarial interventions.

    Science.gov (United States)

    Zenonos, Zenon A; Dummler, Sara K; Müller-Sienerth, Nicole; Chen, Jianzhu; Preiser, Peter R; Rayner, Julian C; Wright, Gavin J

    2015-07-27

    Plasmodium falciparum is the parasite responsible for the most lethal form of malaria, an infectious disease that causes a large proportion of childhood deaths and poses a significant barrier to socioeconomic development in many countries. Although antimalarial drugs exist, the repeated emergence and spread of drug-resistant parasites limit their useful lifespan. An alternative strategy that could limit the evolution of drug-resistant parasites is to target host factors that are essential and universally required for parasite growth. Host-targeted therapeutics have been successfully applied in other infectious diseases but have never been attempted for malaria. Here, we report the development of a recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1 inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established P. falciparum blood-stage infection with no overt toxicity in an in vivo infection model. Collectively, our data demonstrate that antibodies or other therapeutics targeting host basigin could be an effective treatment for patients infected with multi-drug resistant P. falciparum. PMID:26195724

  4. Sensitivity and validity of psychometric tests for assessing driving impairment: effects of sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Stefan Jongen

    Full Text Available To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation.Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am.On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT. Large effects sizes were also found in the Divided Attention Test (DAT, the Attention Network Test (ANT, and the test for Useful Field of View (UFOV at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV.From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.

  5. Uncertainty and sensitivity analyses for age-dependent unavailability model integrating test and maintenance

    International Nuclear Information System (INIS)

    Highlights: ► Application of analytical unavailability model integrating T and M, ageing, and test strategy. ► Ageing data uncertainty propagation on system level assessed via Monte Carlo simulation. ► Uncertainty impact is growing with the extension of the surveillance test interval. ► Calculated system unavailability dependence on two different sensitivity study ageing databases. ► System unavailability sensitivity insights regarding specific groups of BEs as test intervals extend. - Abstract: The interest in operational lifetime extension of the existing nuclear power plants is growing. Consequently, plants life management programs, considering safety components ageing, are being developed and employed. Ageing represents a gradual degradation of the physical properties and functional performance of different components consequently implying their reduced availability. Analyses, which are being made in the direction of nuclear power plants lifetime extension are based upon components ageing management programs. On the other side, the large uncertainties of the ageing parameters as well as the uncertainties associated with most of the reliability data collections are widely acknowledged. This paper addresses the uncertainty and sensitivity analyses conducted utilizing a previously developed age-dependent unavailability model, integrating effects of test and maintenance activities, for a selected stand-by safety system in a nuclear power plant. The most important problem is the lack of data concerning the effects of ageing as well as the relatively high uncertainty associated to these data, which would correspond to more detailed modelling of ageing. A standard Monte Carlo simulation was coded for the purpose of this paper and utilized in the process of assessment of the component ageing parameters uncertainty propagation on system level. The obtained results from the uncertainty analysis indicate the extent to which the uncertainty of the selected

  6. Optimal nondestructive test design for maximum sensitivity and minimal redundancy for applications in material characterization

    Science.gov (United States)

    Notghi, Bahram; Brigham, John C.

    2013-12-01

    An approach to nondestructive test (NDT) design for material characterization and damage identification in structural components, and more generally in solid continua, is presented and numerically tested. The proposed NDT design approach is based on maximizing a measure of the sensitivity of the test responses to changes in the material properties of the structure while also maximizing a measure of the difference in the response components. As such, the optimally designed NDT provides significant improvement in the ability to solve subsequent inverse characterization problems by extracting the maximum amount of non-redundant information from the system to increase the inverse solution observability. The NDT design approach is theoretically able to include any and all possible design aspects, such as the placement of sensors and actuators and determination of actuation frequency, among others. Through simulated test problems based on the characterization of damage in aluminum structural components utilizing steady-state dynamic surface excitation and localized measurements of displacement, the proposed NDT design approach is shown to provide NDT designs with significantly higher measurement sensitivity as well as lower information redundancy when compared to alternate test approaches. More importantly, the optimized NDT methods are shown to provide consistent and significant improvement in the ability to accurately inversely characterize variations in the Young’s modulus distributions for the simulated test cases considered.

  7. Antimalarial drug quality in the most severely malarious parts of Africa - a six country study.

    Directory of Open Access Journals (Sweden)

    Roger Bate

    Full Text Available A range of antimalarial drugs were procured from private pharmacies in urban and peri-urban areas in the major cities of six African countries, situated in the part of that continent and the world that is most highly endemic for malaria. Semi-quantitative thin-layer chromatography (TLC and dissolution testing were used to measure active pharmaceutical ingredient content against internationally acceptable standards. 35% of all samples tested failed either or both tests, and were substandard. Further, 33% of treatments collected were artemisinin monotherapies, most of which (78% were manufactured in disobservance of an appeal by the World Health Organisation (WHO to withdraw these clinically inappropriate medicines from the market. The high persistence of substandard drugs and clinically inappropriate artemisinin monotherapies in the private sector risks patient safety and, through drug resistance, places the future of malaria treatment at risk globally.

  8. Testing the recent snow drought as an analog for climate warming sensitivity of Cascades snowpacks

    Science.gov (United States)

    Cooper, Matthew G.; Nolin, Anne W.; Safeeq, Mohammad

    2016-08-01

    Record low snowpack conditions were observed at Snow Telemetry stations in the Cascades Mountains, USA during the winters of 2014 and 2015. We tested the hypothesis that these winters are analogs for the temperature sensitivity of Cascades snowpacks. In the Oregon Cascades, the 2014 and 2015 winter air temperature anomalies were approximately +2 °C and +4 °C above the climatological mean. We used a spatially distributed snowpack energy balance model to simulate the sensitivity of multiple snowpack metrics to a +2 °C and +4 °C warming and compared our modeled sensitivities to observed values during 2014 and 2015. We found that for each +1 °C warming, modeled basin-mean peak snow water equivalent (SWE) declined by 22%–30%, the date of peak SWE (DPS) advanced by 13 days, the duration of snow cover (DSC) shortened by 31–34 days, and the snow disappearance date (SDD) advanced by 22–25 days. Our hypothesis was not borne out by the observations except in the case of peak SWE; other snow metrics did not resemble predicted values based on modeled sensitivities and thus are not effective analogs of future temperature sensitivities. Rather than just temperature, it appears that the magnitude and phasing of winter precipitation events, such as large, late spring snowfall, controlled the DPS, SDD, and DSC.

  9. Touch-sensitive colour graphics enhance monitoring of loss-of-coolant accident tests

    International Nuclear Information System (INIS)

    A stand-alone computer-based system with an intelligent colour termimal is described for monitoring parameters during loss-of-coolant accident tests. Colour graphic displays and touch-sensitive control have been combined for effective operator interaction. Data collected by the host MODCOMP II minicomputer are dynamically updated on colour pictures generated by the terminal. Experimenters select system functions by touching simulated switches on a transparent touch-sensitive overlay, mounted directly over the face of the colour screen, eliminating the need for a keyboard. Switch labels and colours are changed on the screen by the terminal software as different functions are selected. Interaction is self-prompting and can be learned quickly. System operation for a complete set of 20 tests has demonstrated the convenience of interactive touchsensitive colour graphics

  10. Test and evaluation of a high-sensitivity assay system for bulk transuranic waste

    International Nuclear Information System (INIS)

    During the past year, we tested and evaluated the performance of an assay system that accommodates 55-gal drums of transuranic waste at Oak Ridge National Laboratory. This neutron assay system provides a routine assay of fissile transuranic isotopes to the 1-mg sensitivity level with a pulsed active neutron interrogation based on the differential dieaway technique. A highly sensitive passive neutron measurement determines the content of spontaneous fission transuranic isotopes in each drum as well as an upper-bound estimate of the total alpha activity. All components of the combined, pulsed active and passive neutron assay system performed well on a routine basis during the test-and-evaluation period. We performed more than 400 combined passive and active assay measurements of waste drums at Oak Ridge. One-fifth of the initial set of waste drums measured contain less than 100 nCi/g of total transuranic isotopes and thus qualify legally as nontransuranic waste

  11. Sensitivity and specificity of the functional hallux limitus test to predict foot function.

    Science.gov (United States)

    Payne, Craig; Chuter, Vivienne; Miller, Kathryn

    2002-05-01

    Functional hallux limitus is an underrecognized entity that generally does not produce symptoms but can result in a variety of compensatory mechanisms that can produce symptoms. Clinically, hallux limitus can be determined by assessing the range of motion available at the first metatarsophalangeal joint while the first ray is prevented from plantarflexing. The aim of this study was to determine the sensitivity and specificity of this clinical test to predict abnormal excessive midtarsal joint function during gait. A total of 86 feet were examined for functional hallux limitus and abnormal pronation of the midtarsal joint during late midstance. The test had a sensitivity of 0.72 and a specificity of 0.66, suggesting that clinicians should consider functional hallux limitus when there is late midstance pronation of the midtarsal joint during gait. PMID:12015407

  12. Maintenance Personnel Performance Simulation (MAPPS) model: description of model content, structure, and sensitivity testing. Volume 2

    International Nuclear Information System (INIS)

    This volume of NUREG/CR-3626 presents details of the content, structure, and sensitivity testing of the Maintenance Personnel Performance Simulation (MAPPS) model that was described in summary in volume one of this report. The MAPPS model is a generalized stochastic computer simulation model developed to simulate the performance of maintenance personnel in nuclear power plants. The MAPPS model considers workplace, maintenance technician, motivation, human factors, and task oriented variables to yield predictive information about the effects of these variables on successful maintenance task performance. All major model variables are discussed in detail and their implementation and interactive effects are outlined. The model was examined for disqualifying defects from a number of viewpoints, including sensitivity testing. This examination led to the identification of some minor recalibration efforts which were carried out. These positive results indicate that MAPPS is ready for initial and controlled applications which are in conformity with its purposes

  13. Food Sensitivity in Children with Acute Urticaria in Skin Prick Test: Single Center Experience

    Directory of Open Access Journals (Sweden)

    Hatice Eke Gungor

    2015-11-01

    Full Text Available Aim: Families of children with acute urticaria often think that there is food allergy in children with urticaria and insist for skin tests. In this study, it was aimed to determine whether skin prick tests are necessary in cases presented with acute urticaria, in whom other causes of acute urticaria are excluded. Material and Method: A test panel involving cow milk, egg white, wheat, hazelnut, peanut, soybean, walnut, sesame, and tuna fish antigens was applied to the children presented with acute urticaria between 1 August 2013 and 1 August 2014, in whom other causes of acute urticaria were excluded and suspected food allergy was reported by parents. Results: Overall, 574 children aged 1-14 years were included to the study. Of the patients, sensitization against at least one food antigen was detected in 22.3% (128/574 of the patients. This rate was found to be 31.9% among those younger than 3 years, while 19.3% in those older than 3 years. Overall, sensitization rates against food allergen in panel were as follows: egg white, 7.3%; wheat, 3.3%; cow milk, 2.7%,; sesame, 2.8%; hazelnut, 2.4%; soybean, 2.3%; peanut, 1.9%, walnut, 1.6%; tuna fish, 1.6%. In general, the history of patients wasn%u2019t compatible with food sensitization detected. Discussion: Sensitization to food allergens is infrequent in children presented with acute urticaria, particularly among those older than 3 years despite expressions of parent and skin prick tests seems to be unnecessary unless strongly suggestive history is present.

  14. Identification of neutron irradiation induced strain rate sensitivity change using inverse FEM analysis of Charpy test

    International Nuclear Information System (INIS)

    A simple methodology how to obtain additional information about the mechanical behaviour of neutron-irradiated WWER 440 reactor pressure vessel steel was developed. Using inverse identification, the instrumented Charpy test data records were compared with the finite element computations in order to estimate the strain rate sensitivity of 15Ch2MFA steel irradiated with different neutron fluences. The results are interpreted in terms of activation volume change

  15. The Robustness and Sensitivity of the Mixed-Dirichlet Bayesian Test for "Independence" in Contingency Tables

    OpenAIRE

    Good, I J; Crook, J. F.

    1987-01-01

    A mixed-Dirichlet prior was previously used to model the hypotheses of "independence" and "dependence" in contingency tables, thus leading to a Bayesian test for independence. Each Dirichlet has a main hyperparameter $\\kappa$ and the mixing is attained by assuming a hyperprior for $\\kappa$. This hyperparameter can be regarded as a flattening or shrinking constant. We here review the method, generalize it and check the robustness and sensitivity with respect to variations in the hyperpriors an...

  16. Sensitivity of Multivariate Tests of the Capital Asset-Pricing Model to the Return Measurement Interval.

    OpenAIRE

    Handa, Puneet; Kothari, S. P.; Wasley, Charles

    1993-01-01

    The capital asset pricing model's (CAPM) primary empirical implication is a positively sloped linear relation between a security's expected rate of return and its relative risk (beta). Recent research indicates that inferences about the risk-return relation are sensitive to the choice of the return measurement interval. The authors perform multivariate tests of the Sharpe-Lintner CAPM using monthly and annual returns on market-value-ranked portfolios. The CAPM is rejected using monthly return...

  17. Consistency and sensitivity of lane change test according to driving simulator characteristics

    OpenAIRE

    BRUYAS, Marie-Pierre; BRUSQUE, Corinne; Tattegrain, Hélène; AURIAULT, Adrien; AILLERIE, Isabelle; DURAZ, Max

    2008-01-01

    The aim, here, is to evaluate consistency and sensitivity of the lane change test (LCT), which is the subject of a proposed ISO standard. The method is intended to estimate driver distraction while a secondary task is being performed, by measuring performance degradation on a primary driving-like task. An experiment was conducted in two experimental contexts: a fixed-base driving simulator and a personal computer (PC) (including pedals and steering wheel), and with two auditory and two visual...

  18. Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions

    OpenAIRE

    Baxter, Nielson T.; Ruffin, Mack T; Rogers, Mary A. M.; Schloss, Patrick D.

    2016-01-01

    Background Colorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90 % chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous...

  19. A rapid, sensitive and reliable diagnostic test for scrub typhus in China

    Directory of Open Access Journals (Sweden)

    Zhang Lijuan

    2011-01-01

    Full Text Available Purpose: To evaluate the performances for detection of IgM and IgG antibodies to Orientia. tsutsugamushi (Ot using a gold conjugate-based rapid diagnostic test (RDT. Materials and Methods: The RDT employing mixture recombinant 56-kDa proteins of O. tsutsugamushi and the mIFA assay was performed on 33 patients from Fujian and Yunnan province respectively and 94 positive sera (36 from Hainan province and 58 from Jiangsu province from convalescent stages of the patients with scrub typhus respectively and 82 negative sera from healthy farmers from Anhui province and Beijing City respectively in 2009. A comparison of the RDT and mIFA assay was performed by using the c2 test and the P level of ≤0.05 was considered to be significant. Results: Among these 94 positive sera from convalescent stages of the illness and 82 sera from control farmers, the specificity of RDT was 100% for both IgM and IgG tests. In 33 cases with scrub typhus, 5 cases were positively detected earlier by RDT than by mIFA for the IgM test, and 2 cases were positive for the IgG test. The sensitivities of RDT were 93.9% and 90.9% for IgM and IgG, respectively. Considering IgM and IgG together, the sensitivity was 100%. The geometric mean titre (GMT of IFA and the RDT assay in diluted sera from confirmed cases were 1:37 versus 1:113 respectively (P<0.001 for IgM test and 1:99 versus 1:279 respectively (P<0.016 for IgG. Conclusions: The RDT was more sensitive than the traditional IFA for the early diagnosis of scrub typhus and was particularly suitable for use in rural areas.

  20. Discovery and optimisation studies of antimalarial phenotypic hits

    Science.gov (United States)

    Mital, Alka; Murugesan, Dinakaran; Kaiser, Marcel; Yeates, Clive; Gilbert, Ian H.

    2015-01-01

    There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09–29 μM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds. PMID:26408453

  1. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol.

    Science.gov (United States)

    Gao, Hongfei; Han, Jing; Yang, Shijia; Wang, Zhenxing; Wang, Lin; Fu, Zhifeng

    2014-08-11

    A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β2-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β2-agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50-40 and 0.10-50 ng mL(-1), with the detection limits of 0.20 and 0.040 ng mL(-1) (S/N=3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β2-agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety. PMID:25066723

  2. Power and sensitivity of alternative fit indices in tests of measurement invariance.

    Science.gov (United States)

    Meade, Adam W; Johnson, Emily C; Braddy, Phillip W

    2008-05-01

    Confirmatory factor analytic tests of measurement invariance (MI) based on the chi-square statistic are known to be highly sensitive to sample size. For this reason, G. W. Cheung and R. B. Rensvold (2002) recommended using alternative fit indices (AFIs) in MI investigations. In this article, the authors investigated the performance of AFIs with simulated data known to not be invariant. The results indicate that AFIs are much less sensitive to sample size and are more sensitive to a lack of invariance than chi-square-based tests of MI. The authors suggest reporting differences in comparative fit index (CFI) and R. P. McDonald's (1989) noncentrality index (NCI) to evaluate whether MI exists. Although a general value of change in CFI (.002) seemed to perform well in the analyses, condition specific change in McDonald's NCI values exhibited better performance than a single change in McDonald's NCI value. Tables of these values are provided as are recommendations for best practices in MI testing. PMID:18457487

  3. Natural products as starting points for future anti-malarial therapies: going back to our roots?

    Directory of Open Access Journals (Sweden)

    Wells Timothy NC

    2011-03-01

    Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal

  4. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    Energy Technology Data Exchange (ETDEWEB)

    Dumazert, Jonathan, E-mail: jonathan.dumazert@cea.fr [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Méchin, Laurence [CNRS, UCBN, Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen, 14050 Caen (France)

    2015-09-21

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.

  5. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    International Nuclear Information System (INIS)

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude

  6. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    Science.gov (United States)

    Dumazert, Jonathan; Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane; Méchin, Laurence

    2015-09-01

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.

  7. Potential antimalarials from African natural products: a review

    Directory of Open Access Journals (Sweden)

    Bashir Lawal

    2015-12-01

    Full Text Available Ethnopharmacological relevance: Malaria remains an overwhelming infectious disease with significant health challenges in African and other endemic countries globally. Resistance to antimalarial drugs has become one of the most momentous challenges to human health and thus has necessitated the hunt for new and effective drugs. Consequently, few decades have witnessed a surfeit of research geared to validate the effectiveness of commonly used traditionally medicines against malaria fever. The present review work focuses on documenting natural products from African whose activity has been reported in-vivo or invi-tro against malaria parasite. Methods: Literature was collected using electronic search of published articles (Google Scholar, PubMed, Medline, Sciencedirect, Science domain that report on antiplasmodial activity of natural products from differernts Africa region. Results: A Total of 652 plant taxa from 146 families, 134 isolated antimalarial compounds from 39 plants species, 2 herbal formulations and 4 insect/products were found to be reported in literature from 1996 to 2015. Plants species from family Asteraceae (11.04%, Fababceae (8.128%, Euphorbiaceae (5.52%, Rubiaceas (5.52% and Apocyanaceae (5.214%, have received more scientific validation than others. Conclusion: African natural products possess remarkable healing properties as revealed in the various citations as promising antimalarial agents. Some of these natural products from Africa demonstrate high, promising or low activities against plasmodium parasite. This study also shows that natural products from Africa have a huge amount of novel antimalarial compounds that could serve as a leads for the development of new and effective antiplasmodial drugs. However, in a view of bridging the gap in knowledge, clinical validation of these natural products is of paramount importance. [J Intercult Ethnopharmacol 2015; 4(4.000: 318-343

  8. Drug resistance genomics of the antimalarial drug artemisinin

    OpenAIRE

    Elizabeth A Winzeler; Manary, Micah J

    2014-01-01

    Across the globe, over 200 million annual malaria infections result in up to 660,000 deaths, 77% of which occur in children under the age of five years. Although prevention is important, malaria deaths are typically prevented by using antimalarial drugs that eliminate symptoms and clear parasites from the blood. Artemisinins are one of the few remaining compound classes that can be used to cure multidrug-resistant Plasmodium falciparum infections. Unfortunately, clinical trials from Southeast...

  9. Antimicrobial peptides: a new class of antimalarial drugs?

    Directory of Open Access Journals (Sweden)

    Nuno eVale

    2014-12-01

    Full Text Available A range of antimicrobial peptides (AMP exhibit activity on malaria parasites, Plasmodium spp, in their blood or mosquito stages, or both. These peptides include a diverse array of both natural and synthetic molecules varying greatly in size, charge, hydrophobicity and secondary structure features. Along with an overview of relevant literature reports regarding AMP that display antiplasmodial activity, this review makes a few considerations about those molecules as a potential new class of antimalarial drugs.

  10. Antimalarial drug resistance in Africa: key lessons for the future

    OpenAIRE

    Takala-Harrison, Shannon; Laufer, Miriam K

    2015-01-01

    Drug-resistant parasites repeatedly arise as a result of widespread use of antimalarial drugs and have contributed significantly to the failure to control and eradicate malaria throughout the world. In this review, we describe the spread of resistance to chloroquine and sulfadoxine–pyrimethamine, two old drugs that are no longer used owing to high rates of resistance, and examine the effect of the removal of drug pressure on the survival of resistant parasites. Artemisinin-resistant malaria i...

  11. Intermittent Preventive Antimalarial Treatment for Children with Anaemia.

    OpenAIRE

    Athuman, Mwaka; Kabanywanyi, Abdunoor M; Rohwer, Anke C

    2015-01-01

    Background Anaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected. Although the causes for anaemia are multifactorial, malaria has been linked to anaemia in children living in malaria-endemic areas. Administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, since it could protect children from new Plasmodium parasite infection (the parasites tha...

  12. Revisiting the Role of Potassium Sensitivity Testing and Cystoscopic Hydrodistention for the Diagnosis of Interstitial Cystitis

    Science.gov (United States)

    Jiang, Yuan-Hong; Jhang, Jia-Fong; Kuo, Hann-Chorng

    2016-01-01

    Objectives To revisit the diagnostic roles of cystoscopic hydrodistention and the potassium sensitivity test (PST) for the diagnosis of interstitial cystitis (IC). Methods We prospectively enrolled 214 patients clinically diagnosed with IC, 125 non-IC patients who underwent video urodynamic studies and PST, and another 144 non-IC patients who underwent cystoscopic hydrodistention before transurethral surgery. The sensitivity, specificity, and positive and negative predictive values were calculated for the PST and glomerulations after cystoscopic hydrodistention. Results After cystoscopic hydrodistention, glomerulations developed in 211/214 (98.6%) IC patients and 61/144 (42.4%) of the non-IC patients including patients with stones (45/67, 67%), hematuria (2/5, 40%), and stress urinary incontinence (SUI) (6/17, 35%). When positive glomerulation was defined as grade 2 or more, the sensitivity was 61.7%. The PST was positive in 183/214 (85.5%) IC patients and 7/17 (41%) with hypersensitive bladder, 7/32 (22%) with detrusor overactivity, 5/27 (18%) with SUI, 2/21 (10%) with lower urinary tract symptoms, and 2/25 (8%) with bladder outlet obstruction. The PST had a sensitivity of 85.5% and a specificity of 81.6% for diagnosis of IC. IC patients with a positive PST had a significantly smaller urgency sensation capacity, smaller voided volume, and greater bladder pain score. Conclusions Both the PST and glomerulations after hydrodistention are sensitive indicators of IC, but the specificity of glomerulations in the diagnosis of IC is lower than that of the PST. A positive PST is associated with a more hypersensitive bladder and bladder pain, but not the grade of glomerulations in IC patients. Neither test provided 100% diagnostic accuracy for IC, we might select patients into different subgroups based on different PST and hydrodistention results, not for making a diagnosis of IC but for guidance of different treatments. PMID:26999787

  13. Antimalarials and the fight against malaria in Brazil

    Directory of Open Access Journals (Sweden)

    Luiz MA Carmargo

    2009-04-01

    Full Text Available Luiz MA Carmargo1, Saulo de Oliveira2, Sergio Basano3, Célia RS Garcia21ICBV-USP, Monte Negro, Rondônia, Brasil; 2Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, SP, Brazil; 3CEMETRON, Porto Velho, Guaporé, BrazilAbstract: Malaria, known as the “fevers,” has been treated for over three thousand years in China with extracts of plants of the genus Artemisia (including Artemisia annua, A. opiacea, and A. lancea from which the active compound is artemisin, a sesquiterpene that is highly effective in the treatment of the disease, especially against young forms of the parasite. South American Indians in the seventeenth century already used an extract of the bark of chinchona tree, commonly named “Jesuits’ powder.” Its active compound was isolated in 1820 and its use spread all over the world being used as a prophylactic drug during the construction of the Madeira–Mamoré railroad in the beginning of the twentieth century. During the 1920s to the 1940s, new antimalarial drugs were synthesized to increase the arsenal against this parasite. However, the parasite has presented systematic resistence to conventional antimalarial drugs, driving researchers to find new strategies to treat the disease. In the present review we discuss how Brazil treats Plasmodium-infected patients.Keywords: Plasmodium falciparum, malaria, antimalarials, calcium

  14. Review of pyronaridine anti-malarial properties and product characteristics

    Directory of Open Access Journals (Sweden)

    Croft Simon L

    2012-08-01

    Full Text Available Abstract Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.

  15. Anti-Malarial Plants of Jonai, India: an Ethnobotanical Approach

    Directory of Open Access Journals (Sweden)

    Tonlong WANGPAN

    2016-03-01

    Full Text Available North-East India represents a unique ecosystem with treasured medicinal plant wealth closely related with Folk medicines. A large number of plants having medicinal properties and their folk uses have remained confined to the natives of this region. The tribal community of Jonai, Assam was explored to expose the indigenous herbal remedy for malaria. Sixteen antimalarial plants belonging to 13 families were reported. The analysis revealed highest fidelity level (FL value for Ajuga integrifolia (100% followed by Ricinus communis (94%, Alstonia scholaris (88%, Oroxylum indicum (86% and Achyranthes aspera (82%. The percentage of respondent’s knowledge (PRK about anti-malarial plants showed Alstonia scholaris as the most commonly known antimalarial species (53% within this region. Preference ranking (PR unveiled eight species to be very effective against malarial parasite, which includes Allium sativum, Artemisia indica, Azadirachta indica, Carica papaya, Clerodendrum glandulosum, Ocimum tenuiflorum, Oroxylum indicum, Piper longum and Piper nigrum. All medicine preparations are made using water as the medium and are orally administered in the form of crude extract, powder, juice and decoction. Overall analysis suggested Ajuga integrifolia, Achyranthes aspera, Alstonia scholaris, Artemisia indica, Oroxylum indicum and Ricinus communis to be used for the development of novel, economical, effective and ecofriendly herbal formulations for healthcare management.

  16. Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Svenson, M; Theander, T G;

    1987-01-01

    Effect of pyrimethamine, an antimalarial antifolate, and of mefloquine, chloroquine, and quinine, which belong to the quinoline group of antimalarials, on proliferation and interleukin 2 (IL-2) production of human lymphocytes was studied in vitro. Pyrimethamine at concentrations above therapeutic...... action on human mononuclear cells of the various antimalarial drugs and the potential adverse effects of antimalarial chemotherapy are discussed....... at concentrations twice as high as those required to suppress lymphocyte proliferation. Addition of exogenous IL-2 only partially reversed the suppressive effect on lymphocyte proliferation. Delayed addition of the quinolines decreased their suppressive effect, but not completely. The mechanisms of...

  17. Sensitivity, specificity and predictive values of immunochromatographic strip test in diagnosis of childhood kala-azar.

    Science.gov (United States)

    Rouf, M A; Rahman, M E; Islam, M N; Islam, M N; Ferdous, N N; Hossain, M A

    2009-01-01

    In Bangladesh, the total population at risk for kala-azar exceeds 20 million (18%) living in 88 Thana (19%) of 27 districts (42%). A confirmatory diagnosis of visceral leishmaniasis (kala-azar) is done by demonstration of the parasite (LD body) in organ aspirates or tissue biopsy sample, an invasive procedure with relatively low sensitivity. To assess the diagnostic usefulness of ICT for antibody against the leishmanial antigen rK39 & its feasibility for use under field conditions (rural areas). An experimental study conducted during January, 2003 to July, 2003 in pediatrics department of MMCH including 60 confirmedly diagnosed KA cases & 60 controls having diseases other than KA. One drop of peripheral blood is applied to the nitrocellulose strip & 3 drops of test buffer is added to the dried blood. Observing 2 visible bands indicates presence of IgG anti-K39. The rK39 strip test was positive in 57 out of 60 confirmed KA case diagnosed by LD body demonstration in splenic or bone marrow aspirate. The estimated sensitivity was 95%. One control diagnosed as other than KA had positive strip test but negative aspirate smear. The estimated specificity of the strip test was 98.3%. The predictive value of a positive result is 98.3% & that of a negative result is 93.5%. rK39 strip test is highly sensitive & specific in our situation & it can be used as a simple & the best method for diagnosis of KA in rural areas. PMID:19377416

  18. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hongfei; Han, Jing; Yang, Shijia; Wang, Zhenxing; Wang, Lin; Fu, Zhifeng, E-mail: fuzf@swu.edu.cn

    2014-08-11

    Graphical abstract: A multianalyte immunochromatographic test strip was developed for the rapid detection of two β{sub 2}-agonists. Due to the application of chemiluminescent detection, this quantitative method shows much higher sensitivity. - Highlights: • An immunochromatographic test strip was developed for detection of multiple β{sub 2}-agonists. • The whole assay process can be completed within 20 min. • The proposed method shows much higher sensitivity due to the application of CL detection. • It is a portable analytical tool suitable for field analysis and rapid screening. - Abstract: A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β{sub 2}-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β{sub 2}-agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50–40 and 0.10–50 ng mL{sup −1}, with the detection limits of 0.20 and 0.040 ng mL{sup −1} (S/N = 3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β{sub 2}-agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety.

  19. A sensitive chromatographic strip test for the rapid detection of enrofloxacin in chicken muscle.

    Science.gov (United States)

    Chen, Xuelan; Xu, Hengyi; Lai, Weihua; Chen, Yuan; Yang, Xiaohui; Xiong, Yonghua

    2012-01-01

    A sensitive colloidal gold immunochromatography assay using a specific monoclonal antibody was developed for the rapid detection of enrofloxacin (ENR) residues in chicken muscles. Anti-ENR antibodies with high sensitivity and specificity are generated by immunising BALB/c mice with well-characterised ENR-bovine serum albumin conjugate. An orthogonal L₉(3)³ test was designed, and various parameters that influenced the assay performance were investigated and optimised. Under the optimised conditions, the cut-off limits of semi-quantitative test strips for ENR were found to be 3 ng/mL in phosphate-buffered saline and 8 µg/kg in chicken muscle. The ENR test strips showed a 6% cross-reactivity with ciprofloxacin, 3% with norfloxacin, less than 1% with ofloxacin and sarafloxacin and 0.1% with the other eight fluoroquinolones including enoxacin, difloxacin, danofloxacin, pefloxacin, lomefloxacin, sparfloxacin, oxolinic acid and flumequine. Consistent results are produced from the parallel analysis of ENR-contaminated chicken muscle extracts using test strips and ELISA. PMID:22243423

  20. Sensitivity and specificity of asymmetric recall on WADA test to predict outcome after temporal lobectomy.

    Science.gov (United States)

    Lancman, M E; Benbadis, S; Geller, E; Morris, H H

    1998-02-01

    Some reports suggest that the intracarotid amobarbital test (IAT) is useful for predicting good seizure outcome after temporal lobectomy. The sensitivity, specificity, and predictive value of the IAT in this condition has not been previously studied. We designed this study to establish the value of memory recall asymmetry on the IAT as a predictor of outcome after temporal lobectomy. We studied memory recall on the IAT in 108 consecutive patients with intractable epilepsy who underwent presurgical evaluation for temporal lobectomy and had at least 1 year follow up after surgery. At a level of 30% asymmetry of recall, specificity for favorable outcome (Engel Class I and II) was 100% (95% confidence interval [CI], 85 to 100), sensitivity 51% (95% CI, 40 to 62), positive predictive value 100% (95% CI, 92 to 100), and negative predictive value 34% (95% CI, 23 to 47). At the same level of asymmetry, specificity for seizure-free outcome (Engel Class I) was 88% (95% CI, 68-95), sensitivity 37% (95% CI, 40 to 64), positive predictive value 87% (95% CI, 71 to 96), and negative predictive value 38% (95% CI, 27 to 50). Asymmetric recall on the IAT is highly specific but not very sensitive in predicting outcome after temporal lobectomy. PMID:9484371

  1. Development and validation of animal-free test methods to predict the skin sensitizing potential of chemicals

    OpenAIRE

    Bauch, Caroline D.

    2013-01-01

    Skin sensitization is the development of the allergic contact dermatitis caused by chemicals. Regulatory accepted methods to assess skin sensitizing potential of chemicals are animal based tests, but increasing interest in animal welfare presses the development of animal-free methods. The aim of this work was the development, establishment and validation of several alternative methods to animal testing to predict the skin sensitizing potential of chemicals. Therefore several methods reflectin...

  2. Sensitivity of field tests, serological and molecular techniques for Plum Pox Virus detection in various tissues

    Directory of Open Access Journals (Sweden)

    Mojca VIRŠČEK MARN

    2015-12-01

    Full Text Available Sensitivity of field tests (AgriStrip  and Immunochromato, DAS-ELISA, two step RT-PCR and real-time RT-PCR for Plum pox virus (PPV detection was tested in various tissues of apricot, peach, plum and damson plum trees infected with isolates belonging to PPV-D, PPV-M or PPV-Rec, the three strains present in Slovenia. Flowers of apricot and plum in full bloom proved to be a very good source for detection of PPV. PPV could be detected with all tested techniques in symptomatic parts of leaves in May and with one exception even in the beginning of August, but it was not detected in asymptomatic leaves using field tests, DAS-ELISA and partly also molecular techniques. PPV was detected only in some of the samples of asymptomatic parts of the leaves with symptoms and of stalks by field tests and DAS-ELISA. Infections were not detected in buds in August using field tests or DAS-ELISA. Field tests are useful for confirmation of the PPV infection in symptomatic leaves, but in tissues without symptoms DAS-ELISA should be combined or replaced by molecular techniques.

  3. Sensitivity testing practice on pre-processing parameters in hard and soft coupled modeling

    Directory of Open Access Journals (Sweden)

    Z. Ignaszak

    2010-01-01

    Full Text Available This paper pays attention to the problem of practical applicability of coupled modeling with the use of hard and soft models types and necessity of adapted to that models data base possession. The data base tests results for cylindrical 30 mm diameter casting made of AlSi7Mg alloy were presented. In simulation tests that were applied the Calcosoft system with CAFE (Cellular Automaton Finite Element module. This module which belongs to „multiphysics” models enables structure prediction of complete casting with division of columnar and equiaxed crystals zones of -phase. Sensitivity tests of coupled model on the particular values parameters changing were made. On these basis it was determined the relations of CET (columnar-to-equaiaxed transition zone position influence. The example of virtual structure validation based on real structure with CET zone location and grain size was shown.

  4. Nickel contact sensitivity in the guinea pig. An efficient open application test method

    DEFF Research Database (Denmark)

    Nielsen, G D; Rohold, A E; Andersen, Klaus Ejner

    1992-01-01

    Nickel contact sensitivity was successfully induced in guinea pigs using an open epicutaneous application method. Immediately after pretreatment with 1% aqueous sodium lauryl sulfate, upper back skin was treated daily for 4 weeks with 0.3%-3% nickel sulfate in either a 1% lanolin cream (Vaseline, p......H 5 SAD crème) or hydroxypropyl cellulose. Weekly intradermal injections with aluminium potassium sulfate were used as adjuvant. The animals were challenged twice with a one week interval, with nickel sulfate 2% in water and 1% in petrolatum, respectively. The response rates in the test groups treated...... with nickel sulfate 1% or 3% in the lanolin cream or 1% in hydroxypropyl cellulose were significantly different from the response rate in the control group. Considering both readings at both challenges, the frequency of sensitization was 57-93% (8 of 14 to 13 of 14 animals) in the group treated with 1...

  5. Ligand-based virtual screening and in silico design of new antimalarial compounds using nonstochastic and stochastic total and atom-type quadratic maps.

    Science.gov (United States)

    Marrero-Ponce, Yovani; Iyarreta-Veitía, Maité; Montero-Torres, Alina; Romero-Zaldivar, Carlos; Brandt, Carlos A; Avila, Priscilla E; Kirchgatter, Karin; Machado, Yanetsy

    2005-01-01

    Malaria has been one of the most significant public health problems for centuries. It affects many tropical and subtropical regions of the world. The increasing resistance of Plasmodium spp. to existing therapies has heightened alarms about malaria in the international health community. Nowadays, there is a pressing need for identifying and developing new drug-based antimalarial therapies. In an effort to overcome this problem, the main purpose of this study is to develop simple linear discriminant-based quantitative structure-activity relationship (QSAR) models for the classification and prediction of antimalarial activity using some of the TOMOCOMD-CARDD (TOpological MOlecular COMputer Design-Computer Aided "Rational" Drug Design) fingerprints, so as to enable computational screening from virtual combinatorial datasets. In this sense, a database of 1562 organic chemicals having great structural variability, 597 of them antimalarial agents and 965 compounds having other clinical uses, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. This series of compounds was processed by a k-means cluster analysis in order to design training and predicting sets. Afterward, two linear classification functions were derived in order to discriminate between antimalarial and nonantimalarial compounds. The models (including nonstochastic and stochastic indices) correctly classify more than 93% of the compound set, in both training and external prediction datasets. They showed high Matthews' correlation coefficients, 0.889 and 0.866 for the training set and 0.855 and 0.857 for the test one. The models' predictivity was also assessed and validated by the random removal of 10% of the compounds to form a new test set, for which predictions were made using the models. The overall means of the correct classification for this process (leave group 10% full-out cross validation) using the equations with nonstochastic

  6. Perception of basic tastes and threshold sensitivity during testing of selected judges

    Directory of Open Access Journals (Sweden)

    Peter Zajác

    Full Text Available Normal 0 false false false SK JA X-NONE The sense of taste is one of the most important human senses. Alteration in taste perception can greately interfere to our lives, because it influences our dietary habits and consequently general human health. Many physiological and external factors can cause the loss of taste perception. These factors include for example certain diseases, the side effect of the use of certain medicaments, head trauma, gender, dietary habbits, smoking, role of saliva, age, stress and many more. In this paper we are discussing perception of basic tastes and treshold sensitivity during testing of selected groupe of 500 sensory judges. A resolution taste test and sensitivity treshold test were performed using basic tastes (sour, bitter, salty, sweet, umami, astringent, metallic. We have found that the perception of basic tastes decreese with human age. Smoking leads to significant errors in the determination of basic tastes. Different mistakes occures in different age categories. This study suggests further researches, investigating various factors influencing taste perception.  doi:10.5219/259

  7. In Vitro Cardiovascular Effects of Dihydroartemisin-Piperaquine Combination Compared with Other Antimalarials

    Science.gov (United States)

    Crumb, William; Pace, Silvia; Ubben, David; Wible, Barb; Yan, Gan-Xin; Funck-Brentano, Christian

    2012-01-01

    The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (Cmax), were expressed as the fold of that particular effect with respect to their Cmax. The following tests were used at 37°C: hERG (human ether-à-go-go-related gene) blockade and trafficking, rabbit heart ventricular preparations, and sodium and slow potassium ion current interference (INa and IKs, respectively). Chloroquine, halofantrine, mefloquine, and lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide, lumefantrine, and the combination of artemether-lumefantrine were used in the rabbit heart ventricular preparations, hERG trafficking studies, and INa and IKs analyses. A proper reference was used in each test. In hERG studies, the high 50% inhibitory concentration (IC50) of halofantrine, which was lower than its Cmax, was confirmed. All the other compounds blocked hERG, with IC50s ranging from 3- to 30-fold their Cmaxs. In hERG trafficking studies, the facilitative effects of chloroquine at about 30-fold its Cmax were confirmed and DHA blocked it at a concentration about 300-fold its Cmax. In rabbit heart ventricular preparations, dofetilide, used as a positive control, revealed a high risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a significant proarrhythmic risk. Only chloroquine blocked the INa ion current and did so at about 30-fold its Cmax. No effect on IKs was detected. In conclusion, despite significant hERG blockade, DHA-PQP and artemether-lumefantrine do not appear to induce potential torsadogenic effects in vitro, affect hERG trafficking, or block sodium and slow potassium ion currents. PMID:22391528

  8. In Vivo Antimalarial Activity of Annona muricata Leaf Extract in Mice Infected with Plasmodium berghei.

    Science.gov (United States)

    Somsak, Voravuth; Polwiang, Natsuda; Chachiyo, Sukanya

    2016-01-01

    Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of the Annona muricata aqueous leaf extract in Plasmodium berghei infected mice. Aqueous leaf extract of A. muricata was prepared and tested for acute toxicity in mice. For efficacy test in vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 10(7) parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found that A. muricata aqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, the A. muricata aqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment. PMID:27092277

  9. Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

    OpenAIRE

    Cupo, Palmira; AZEVEDO-MARQUES Marisa M. de; SARTI Willy; HERING Sylvia Evelyn

    2001-01-01

    An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the Univ...

  10. Patch test dose-response study: polysensitized individuals do not express lower elicitation thresholds than single/double-sensitized individuals

    DEFF Research Database (Denmark)

    Carlsen, B C; Fischer, Louise Arup; Sosted, H;

    2009-01-01

    compare elicitation dose-response curves and elicitation thresholds in a polysensitized vs. a single/double-sensitized group for allergens to which the test subjects were already sensitized. PATIENTS/METHODS: Fifty-one patients (13 polysensitized and 38 single/double-sensitized) were patch tested with...... nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group for...

  11. A high-sensitivity and quasi-linear capacitive sensor for nanomechanical testing applications

    International Nuclear Information System (INIS)

    The design, modeling, fabrication and characterization of triplate differential capacitive sensors employed in novel on-chip tensile and compression material testing systems are reported, where the capacitive sensors are integrated to measure the load on the specimen or the specimen deformation. Analytical expressions for studying stability, linearity and sensitivity, including the effect of the electrostatic force generated by the excitation signal on the sensing electrodes, are derived for the first time and discussed for quasi-static applications. The possible influence of the electron beam of an electron microscope on the capacitance measurement is also analyzed. The in-plane suspension stiffness of the fabricated device is determined by a resonance method performed inside a scanning electron microscope and used for pull-in voltage prediction. Sensitivity and linearity are extracted from capacitance-to-displacement measurements and agree well with analytical and finite element analysis results. The fabricated capacitive sensors show a high sensitivity of 0.61 fF nm−1 within a quasi-linear moving range of 2250 nm, which yields a displacement resolution of 1 nm and a load resolution of 34 nN

  12. In vivo antimalarial activity of extracts of Tanzanian medicinal plants used for the treatment of malaria.

    Science.gov (United States)

    Nondo, Ramadhani S O; Erasto, Paul; Moshi, Mainen J; Zacharia, Abdallah; Masimba, Pax J; Kidukuli, Abdul W

    2016-01-01

    Plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. The aim of this study was to evaluate in vivo antimalarial activity of four plants; Erythrina schliebenii Harms, Holarrhena pubescens Buch-Ham, Phyllanthus nummulariifolius Poir, and Caesalpinia bonducella (L.) Flem used for treatment of malaria in Tanzania. In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injection via tail vein with 2 × 10(7) erythrocytes infected with Plasmodium berghei ANKA. Extracts were administered orally, once daily, for a total of four daily doses from the day of infection. Chloroquine (10 mg/kg/day) and solvent (5 mL/kg/day) were used as positive and negative controls, respectively. The extracts of C. bonducella, E. schliebenii, H. pubescens, and P. nummulariifolius exhibited dose-dependent suppression of parasite growth in vivo in mice, with the highest suppression being by C. bonducella extract. While each of the plant extracts has potential to yield useful antimalarial compounds, the dichloromethane root extract of C. bonducella seems to be the most promising for isolation of active antimalarial compound(s). In vivo antimalarial activity presented in this study supports traditional uses of C. bonducella roots, E. schliebenii stem barks, H. pubescens roots, and P. nummulariifolius for treatment of malaria. PMID:27144154

  13. Fabrication and testing of a MEMS platform for characterization of stimuli-sensitive hydrogels

    International Nuclear Information System (INIS)

    A microelectromechanical systems (MEMS) platform for hydrogel benchmarking was designed, fabricated and tested. This MEMS platform is a testbed for the characterization of stimuli-sensitive hydrogels at the micrometer scale, which makes it a useful tool for developing and benchmarking different hydrogels in a realistic usage environment. The platform allows the application of chemical and thermal stimuli and the monitoring of the hydrogel’s swelling or shrinking by visual methods as well as by an embedded conductometric sensing mechanism. Such a platform allows measurements on a small scale and is especially useful to make a realistic assessment of the behavior of a gel after going through a microfabrication process. Several hydrogels were tested utilizing this proposed MEMS platform to prove the concept. (technical note)

  14. Results of Antibiotic Sensitivity Tests of Bacteria Causing Acute Otitis Media

    Directory of Open Access Journals (Sweden)

    M Khajeh Karameddini

    2000-07-01

    Full Text Available In a period of 12 months 241 children (2-12 years old with Otitis Media were examined. 98 bacteria were isolated from Otitis Media discharge and tested for sensitivity against 13 generic antibiotics. The disk-agar diffusion and macrodilution both methods were used for these tests. Staphylococcus aureus had the highest and streptococcus pneumonia the lowest rate of occurrence. Otitis Media cases caused by merely a single bacterium were 12 fold more than those caused by two bacteria and 4 fold more than those caused by more than two bacteria. The antibacterial efficacy of carbenicillin, gentamicin, kanamycin and amikacin was higher than that of other antibiotics in disk-agar diffusion method. The MIC rates of cefoperazone against four most frequently encountered bacteria were higher than that of Mezlocillin.

  15. Clutter sensitivity test under controlled field conditions Resonant Microstrip Patch Antenna (RMPA) sensor technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-06-27

    Theoretical research, controlled laboratory tests, and these field test results show that nonmetallic (and metallic) shallowly buried objects can be detected and imaged with the Resonant Microstrip Patch Antenna (RMPA) sensor. The sensor can be modeled as a high Q cavity which capitalizes on its resonant condition sensitivity to scattered waves from buried objects. When the RMPA sensor is swept over a shallowly buried object, the RMPA fed-point impedance (resistance), measured with a Maxwell bridge, changes by tens of percent. The significant change in unprocessed impedance data can be presented in two-dimensional and three-dimensional graphical displays over the survey area. This forms silhouette images of the objects without the application of computationally intensive data processing algorithms. Because RMPA employed electromagnetic waves to illuminate the shallowly buried object, a number of questions and issues arise in the decision to fund or deny funding of the reconfiguration of the RMPA technology into a nonmetallic (metallic) land mine detector.

  16. Synthesis, Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4-aminoquinoline-1,3,5-triazine Derivatives Against Wild and Mutant Malaria Parasites.

    Science.gov (United States)

    Bhat, Hans Raj; Singh, Udaya Pratap; Gahtori, Prashant; Ghosh, Surajit Kumar; Gogoi, Kabita; Prakash, Anil; Singh, Ramendra K

    2015-09-01

    A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules. PMID:25487527

  17. Self-healing mortar with pH-sensitive superabsorbent polymers: testing of the sealing efficiency by water flow tests

    Science.gov (United States)

    Gruyaert, Elke; Debbaut, Brenda; Snoeck, Didier; Díaz, Pilar; Arizo, Alejandro; Tziviloglou, Eirini; Schlangen, Erik; De Belie, Nele

    2016-08-01

    Superabsorbent polymers (SAPs) have potential to be used as healing agent in self-healing concrete due to their property to attract moisture from the environment and their capacity to promote autogenous healing. A possible drawback, however, is their uptake of mixing water during concrete manufacturing, resulting in an increased volume of macro-pores in the hardened concrete. To limit this drawback, newly developed SAPs with a high swelling and pH-sensitiveness were developed and tested within the FP7 project HEALCON. Evaluation of their self-sealing performance occurred through a water permeability test via water flow, a test method also developed within HEALCON. Three different sizes of the newly developed SAP were compared with a commercial SAP. Swelling tests in cement filtrate solution indicated that the commercial and in-house synthesized SAPs performed quite similar, but the difference between the swelling capacity at pH 9 and pH 13 is more pronounced for the self-synthesized SAPs. Moreover, in comparison to the commercial SAPs, less macro-pores are formed in the cement matrix of mixes with self-synthesized SAPs and the effect on the mechanical properties is lower, but not negligible, when using high amounts of SAPs. Although the immediate sealing effect of cracks in mortar was the highest for the commercial SAPs, the in-house made SAPs with a particle size between 400 and 600 μm performed the best with regard to crack closure (mainly CaCO3 precipitation) and self-sealing efficiency, after exposing the specimens to 28 wet–dry cycles. Some specimens could even withstand a water pressure of 2 bar.

  18. Sensitization to Aeroallergens in Patients with Respiratory Allergies Based on Skin-Prick Test Results

    Directory of Open Access Journals (Sweden)

    G Bejtullahu

    2012-10-01

    Full Text Available Background: The aim of this study was to identify the most common aeroallergens in patients with asthma and rhinitis.Methods: The study enrolled 102 participants including 64 patients with respiratory allergies (among them 15 were clinically diagnosed as asthma patients, 41 with rhinitis, 8 were both and 38 healthy controls. All of participants were subject of skin prick tests (SPT with series of common allergenic extracts. Sera from all participants were tested for total IgE and eosinophil count. To measure airflow limitation and reversibility in asthma patients the pulmonary function testing were carried out.Results: M/F ratio was 1:1.6 in patients and 1:0.7 in control group with mean age 28.88 year (SD 13.16; range 6 – 55year and 20.47 respectively (SD 1.16; range 19-23 year. The most common risk factors in these patients were total IgE more than 100 IU/ml, eosinophils above 4% and positive family history of atopy. Skin prick testing results showed prevalence rates for allergen groups in this manner: house dust mites 81.3 %, pollens 57.8 %, animal dandruff12.5% and moulds 4.9%. Polysensitization was common in 51.6% of all sensitized patients being positive to more than one group of allergens.Conclusion: House dust mites are the main sensitizing allergens among our allergic patients as well as healthy controls. Next in importance, in all participants, are grasses. This pattern of prevalence was expected based on herbal geography, climate and specially lifestyle. It was also compatible with the results from studies carried out in places with the same habitat.

  19. Testing sensitivity of the LISFLOOD subgrid hydraulic model to SAR image derived information

    Science.gov (United States)

    Wood, Melissa; Bates, Paul; Neal, Jeff; Hostache, Renaud; Matgen, Patrick; Chini, Marco; Giustarini, Laura

    2013-04-01

    There has been much interest in the use of Synthetic Aperture Radar (SAR) images to indirectly estimate flood extent and flood elevation to aid the understanding of fluvial flood inundation processes. SAR remote sensing satellites are capable of all-weather day/night observations that can discriminate between land and smooth open water surfaces over large scales. By combining SAR derived information with 2D hydraulic models and terrain data, the mechanisms of flooding can be better simulated therefore enabling more accurate and reliable flood forecasting. The objective of this study is to test the sensitivity of a LISFLOOD subgrid 2D model to its main parameters (i.e. roughness coefficient, river bathymetry) using SAR derived flood extent maps. Because of SAR imaging techniques and processing steps used to derive the flood information, any SAR-derived flood extent image will contain inherent uncertainty. We therefore use the uncertainty of the SAR information to obtain a range of plausible parameters to test sensitivity of the hydraulic model. LISFLOOD is a distributed 2D model developed at the University of Bristol and designed for use with larger ungauged river catchments. The version used employs a subgrid procedure which allows any size of river channel below that of the grid resolution to be represented. This procedure has been shown to improve hydraulic connectivity within the modelled flooded area and thus improve flood prediction for data sparse areas. A hydrodynamic LISFLOOD subgrid model of the River Severn at Tewkesbury covering a domain area of 50x70km and including the confluence with a major tributary (the River Avon) will be utilised. A complete storm hydrograph will be used as inflow to the model to simulate the full flood event. Surveyed cross section and gauged daily flows are also available for the River Severn. Therefore, the model results using variable parameters can be compared against results obtained from ground observations to further

  20. Postage stamp-sized array sensor for the sensitive screening test of heavy-metal ions.

    Science.gov (United States)

    Zhang, Yu; Li, Xiao; Li, Hui; Song, Ming; Feng, Liang; Guan, Yafeng

    2014-10-01

    The sensitive determination of heavy-metal ions has been widely investigated in recent years due to their threat to the environment and to human health. Among various analytical detection techniques, inexpensive colorimetric testing papers/strips play a very important role. The limitation, however, is also clear: the sensitivity is usually low and the selectivity is poor. In this work, we have developed a postage stamp-sized array sensor composed of nine commercially available heterocyclic azo indicators. Combining filtration-based enrichment with an array of technologies-based pattern-recognition, we have obtained the discrimination capability for seven heavy-metal ions (Hg(2+), Pb(2+), Ag(+), Ni(2+), Cu(2+), Zn(2+), and Co(2+)) at their Chinese wastewater discharge standard concentrations. The allowable detection level of Hg(2+) was down to 0.05 mg L(-1). The heavy-metal ions screening test was readily achieved using a standard chemometric approach. And the array sensor applied well in real water samples. PMID:25068762

  1. Testing of the derivative method and Kruskal-Wallis technique for sensitivity analysis of SYVAC

    International Nuclear Information System (INIS)

    The Kruskal-Wallis method of one-way analysis of variance by ranks has proved successful in identifying input parameters which have an important influence on dose. This technique was extended to test for first order interactions between parameters. In view of a number of practical difficulties and the computing resources required to carry out a large number of runs, this test is not recommended for detecting interactions between parameters. The derivative method of sensitivity analysis examines the partial derivative values of each input parameter with dose at various points across the parameter range. Important input parameters are associated with high derivatives and the results agreed well with previous sensitivity studies. The derivative values also provided information on the data generation distributions to be used for the input parameters in order to concentrate sampling in the high dose region of the parameter space to improve the sampling efficiency. Furthermore, the derivative values provided information on parameter interactions, the feasibility of developing a high dose algorithm and formed the basis for developing a regression equation. (author)

  2. Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

    Directory of Open Access Journals (Sweden)

    Bertocchi Paola

    2007-02-01

    Full Text Available Abstract Background The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. Methods In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. Results The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date; low content of active substance (in one sample; different, non-declared, active substance (in one sample; sub-standard technological properties and very low dissolution profiles (in about 50% of samples. This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. Conclusion This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution

  3. ABSTRACT: CONTAMINANT TRAVEL TIMES FROM THE NEVADA TEST SITE TO YUCCA MOUNTAIN: SENSITIVITY TO POROSITY

    International Nuclear Information System (INIS)

    Yucca Mountain (YM), Nevada, has been proposed by the U.S. Department of Energy as a geologic repository for spent nuclear fuel and high-level radioactive waste. In this study, we investigate the potential for groundwater advective pathways from underground nuclear testing areas on the Nevada Test Site (NTS) to the YM area by estimating the timeframe for advective travel and its uncertainty resulting from porosity value uncertainty for hydrogeologic units (HGUs) in the region. We perform sensitivity analysis to determine the most influential HGUs on advective radionuclide travel times from the NTS to the YM area. Groundwater pathways and advective travel times are obtained using the particle tracking package MODPATH and flow results from the Death Valley Regional Flow System (DVRFS) model by the U.S. Geological Survey. Values and uncertainties of HGU porosities are quantified through evaluation of existing site porosity data and expert professional judgment and are incorporated through Monte Carlo simulations to estimate mean travel times and uncertainties. We base our simulations on two steady state flow scenarios for the purpose of long term prediction and monitoring. The first represents pre-pumping conditions prior to groundwater development in the area in 1912 (the initial stress period of the DVRFS model). The second simulates 1998 pumping (assuming steady state conditions resulting from pumping in the last stress period of the DVRFS model). Considering underground tests in a clustered region around Pahute Mesa on the NTS as initial particle positions, we track these particles forward using MODPATH to identify hydraulically downgradient groundwater discharge zones and to determine which flowpaths will intercept the YM area. Out of the 71 tests in the saturated zone, flowpaths of 23 intercept the YM area under the pre-pumping scenario. For the 1998 pumping scenario, flowpaths from 55 of the 71 tests intercept the YM area. The results illustrate that mean

  4. Sensitization Profile to Allergens in Patients Using Multi-Test II

    Science.gov (United States)

    Maniglia, Sergio Fabricio; Tsuru, Fernanda Miyoko; Santos, Victor Carvalho dos; Ueda, Denis Massatsugu

    2014-01-01

    Introduction Medical intervention in allergies has broadened its perspective, also focusing in the quality of life of patients. Patients are instructed, before using pharmacotherapy agents, to avoid the causal agent. Objective This study aims to analyze the sensitization profile of patients with allergic complaints and identify possible characteristics specific to each age group and gender. Methods A descriptive cross-sectional study included data collected from medical records (from Multi-Test II database, Lincoln Diagnostics Inc. Decatur, Illinois) of 1,912 patients who underwent skin prick test from March to October 2013. Patients were organized and analyzed according to gender, age, and results of the allergens subtypes tested. Results The study was composed of 1,912 patients (60% male and 40% female) of ages between 3 and 87 years. Positive tests were more prevalent in quantity and intensity with the mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, each with 60% of the total analyzed. In second place were pollens, especially Dactylis glomerata and Festuca pratensis. Conclusion The female and male sexes were equally atopic. Fungi and epithelia of dog and cat were not considered potential aeroallergens that could cause symptoms. However, mites are common in Paraná, Brazil. Further studies regarding the pollens are needed, as this study result diverged from the literature. PMID:25992129

  5. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    OpenAIRE

    Wanna Chaijaroenkul; Artitiya Thiengsusuk; Kanchana Rungsihirunrat; Stephen Andrew Ward; Kesara Na-Bangchang

    2014-01-01

    Objective: To investigate possible protein targets for antimalarial activity of Garcinia mangostana Linn. (G. mangostana) (pericarp) in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry (LC/MS/MS). Methods: 3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G. mangostana Linn. (pericarp) at the concentrations of 12μg/mL (IC50 level: concentration that inhibits parasite growth by 50%) and 30 μg/mL (IC90 level...

  6. Home treatment of febrile children with antimalarial drugs in Togo.

    OpenAIRE

    Deming, M. S.; Gayibor, A.; Murphy, K; Jones, T. S.; Karsa, T.

    1989-01-01

    In Togo, the principal strategy for preventing death from malaria in children is prompt treatment of fever with antimalarial drugs. A household survey was conducted in a rural area of south-central Togo in which information was collected from mothers on the treatment received by 507 children under 5 years of age who, according to their mothers, had recently had fever. Altogether, 20% of the children (95% confidence interval (Cl): 15-25%) were seen at a health centre during their illness, whil...

  7. Targeting Plasmodium falciparum Hsp90: Towards Reversing Antimalarial Resistance

    Directory of Open Access Journals (Sweden)

    Dea Shahinas

    2013-02-01

    Full Text Available Malaria continues to exact a great human toll in tropical settings. Antimalarial resistance is rife and the parasite inexorably develops mechanisms to outwit our best drugs, including the now first-line choice, artesunate. Novel strategies to circumvent resistance are needed. Here we detail drug development focusing on heat shock protein 90 and its central role as a chaperone. A growing body of evidence supports the role for Hsp90 inhibitors as adjunctive drugs able to restore susceptibility to traditionally efficacious compounds like chloroquine.

  8. Mono- and bis-thiazolium salts have potent antimalarial activity.

    Science.gov (United States)

    Hamzé, Abdallah; Rubi, Eric; Arnal, Pascal; Boisbrun, Michel; Carcel, Carole; Salom-Roig, Xavier; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Calas, Michèle

    2005-05-19

    Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50)

  9. Cloroquine – miscellaneous properties of the antimalarial drug

    Directory of Open Access Journals (Sweden)

    Robert Jarzyna

    2002-06-01

    Full Text Available Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.

  10. Searching for a more sensitive earthworm species to be used in pesticide homologation tests – A meta-analysis.

    OpenAIRE

    Joimel, Sophie; MAKOWSKI, DAVID; Makowski, Daniel

    2013-01-01

    Pesticide risk assessments include experiments designed to measure the effect of pesticides on earthworms using the Eisenia fetida fetida or Eisenia fetida andrei species. There is no clear consensus in the literature on the sensitivity of different earthworm species to pesticides. We performed a meta-analysis on the sensitivity of several earthworm species to pesticides to determine the most sensitive species, and to discuss their suitability for European homologation tests. A dataset i...

  11. The Brief Kinesthesia test is feasible and sensitive: a study in stroke

    Directory of Open Access Journals (Sweden)

    Alexandra Borstad

    2016-02-01

    Full Text Available BACKGROUND: Clinicians lack a quantitative measure of kinesthetic sense, an important contributor to sensorimotor control of the hand and arm. OBJECTIVES: The objective here was to determine the feasibility of administering the Brief Kinesthesia Test (BKT and begin to validate it by 1 reporting BKT scores from persons with chronic stroke and a healthy comparison group and 2 examining the relationship between the BKT scores and other valid sensory and motor measures. METHOD: Adults with stroke and mild to moderate hemiparesis (N=12 and an age-, gender-, and handedness-matched healthy comparison group (N=12 completed the BKT by reproducing three targeted reaching movements per hand with vision occluded. OTHER MEASURES: the Hand Active Sensation Test (HASTe, Touch-Test(tm monofilament aesthesiometer, 6-item Wolf Motor Function Test (Wolf, the Motor Activity Log (MAL, and the Box and Blocks Test (BBT. A paired t-test compared BKT scores between groups. Pearson product-moment correlation coefficients assessed the relationship between BKT scores and other measures. RESULTS: Post-stroke participants performed more poorly on the BKT than comparison participants with their contralesional and ipsilesional upper extremity. The mean difference for the contralesional upper extremity was 3.7 cm (SE=1.1, t=3.34; p<0.008. The BKT score for the contralesional limb was strongly correlated with the MAL-how much (r=0.84, p=0.001, the MAL-how well (r=0.76, p=0.007, Wolf (r=0.69, p=0.02, and the BBT (r=0.77, p=0.006. CONCLUSIONS: The BKT was feasible to administer and sensitive to differences in reaching accuracy between persons with stroke and a comparison group. With further refinement, The BKT may become a valuable clinical measure of post-stroke kinesthetic impairment.

  12. Development of an umami taste sensitivity test and its clinical use.

    Directory of Open Access Journals (Sweden)

    Shizuko Satoh-Kuriwada

    Full Text Available There is a close relationship between perception of umami, which has become recognized as the fifth taste, and the human physical condition. We have developed a clinical test for umami taste sensitivity using a filter paper disc with a range of six monosodium glutamate (MSG concentrations. We recruited 28 patients with taste disorders (45-78 years and 184 controls with no taste disorders (102 young [18-25 years] and 82 older [65-89 years] participants. Filter paper discs (5 mm dia. were soaked in aqueous MSG solutions (1, 5, 10, 50, 100 and 200 mM, then placed on three oral sites innervated by different taste nerves. The lowest concentration participants correctly identified was defined as the recognition threshold (RT for MSG. This test showed good reproducibility for inter- and intra-observer variability. We concluded that: (1 The RT of healthy controls differed at measurement sites innervated by different taste nerves; that is, the RT of the anterior tongue was higher than that of either the posterior tongue or the soft palate in both young and older individuals. (2 No significant difference in RT was found between young adults and older individuals at any measurement site. (3 The RT of patients with taste disorders was higher before treatment than that of the healthy controls at any measurement site. (4 The RT after treatment in these patients improved to the same level as that of the healthy controls. (5 The cutoff values of RT, showing the highest diagnostic accuracy (true positives + true negatives, were 200 mM MSG for AT and 50 mM MSG for PT and SP. The diagnostic accuracy at these cutoff values was 0.92, 0.87 and 0.86 for AT, PT and SP, respectively. Consequently, this umami taste sensitivity test is useful for discriminating between normal and abnormal umami taste sensations.

  13. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    Science.gov (United States)

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  14. Statins as Potential Antimalarial Drugs: Low Relative Potency and Lack of Synergy with Conventional Antimalarial Drugs▿

    OpenAIRE

    Wong, Rina P. M.; Davis, Timothy M. E.

    2009-01-01

    The in vitro sensitivity of Plasmodium falciparum to atorvastatin and rosuvastatin was assessed using chloroquine-sensitive and chloroquine-resistant strains. Although atorvastatin was more potent, it had weak activity (mean 50% inhibitory concentration of ≥17 μM) and an indifferent interaction with chloroquine and dihydroartemisinin. Bioassay of plasma from an atorvastatin-treated subject showed similar results.

  15. In Vivo Antimalarial Effects of Iranian Flora Artemisia khorassanica against Plasmodium berghei and Pharmacochemistry of its Natural Components

    Directory of Open Access Journals (Sweden)

    M Amini

    2010-02-01

    Full Text Available "nBackground: The aim of this study was to evaluate the antimalarial effects of Iranian flora Artemisia khorassanica against Plasmodium berghei in vivo and pharmacochemistry of its natural components."nMethods: The aerial parts of Iranian flora A. khorasanica were collected at flowering stage from Khorassan Province, northeastern Iran in 2008. They were air-dried at room temperature; powder was macerated in methanol and the extract defatted in refrigerator, filtered, diluted with water, then eluted with n-hexane and finally non-polar components were identified through Gas Chromatography and Mass Spectroscopy (GC-MS. Toxicity of herbal extracts was assessed on naïve NMRI mice, and its anti-malarial efficacy was investigated on infected Plasmodium berghei animals. This is the first ap­plication on A. khorssanica extract for treatment of murine malaria. The significance of differences was determined by Analysis of Variances (ANOVA and Student's t-test using Graph Pad Prism Software."nResults: The herbal extract was successfully tested in vivo for its anti-plasmodial activity through ar­temisin composition, which is widely used as a standard malaria treatment."nConclusion: Although, this study confirmed less anti-malarial effects of A. khorssanica against mur­ine malaria in vivo, how­ever there are some evidences on reducing pathophysiology by this medica­tion. In complementary assay, major components were detected by GC-MS analysis in herbal extract including chrysanthe­none (7.8%, palmitic acid (7.4% and cis-thujone (5.8%.  The most retention indices of the compo­nent are given as n-eicosane, palmitic acid and n-octadecane.

  16. Identification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity

    Directory of Open Access Journals (Sweden)

    Rebecca D. Sandlin

    2014-12-01

    Full Text Available The emergence of drug resistant strains of Plasmodium spp. creates a critical need for the development of novel antimalarials. Formation of hemozoin, a crystalline heme detoxification process vital to parasite survival serves as an important drug target. The quinoline antimalarials including chloroquine and amodiaquine owe their antimalarial activity to inhibition of hemozoin formation. Though in vivo formation of hemozoin occurs within the presence of neutral lipids, the lipophilic detergent NP-40 was previously shown to serve as a surrogate in the β-hematin (synthetic hemozoin formation process. Consequently, an NP-40 mediated β-hematin formation assay was developed for use in high-throughput screening. Here, the assay was utilized to screen 144,330 compounds for the identification of inhibitors of crystallization, resulting in 530 hits. To establish the effectiveness of these target-based β-hematin inhibitors against Plasmodium falciparum, each hit was further tested in cultures of parasitized red blood cells. This effort revealed that 171 of the β-hematin inhibitors are also active against the parasite. Dose–response data identified 73 of these β-hematin inhibitors have IC50 values ⩽5 μM, including 25 compounds with nanomolar activity against P. falciparum. A scaffold-based analysis of this data identified 14 primary scaffolds that represent 46% of the 530 total hits. Representative compounds from each of the classes were further assessed for hemozoin inhibitory activity in P. falciparum infected human erythrocytes. Each of the hit compounds tested were found to be positive inhibitors, while a negative control did not perturb this biological pathway in culture.

  17. New imidazolidinedione derivatives as antimalarial agents

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang; Sathunuru, Ramadas; Luong, ThuLan; Melendez, Victor; Kozar, Michael P.; Lin, Ai J. (Walter Reed)

    2012-04-30

    A series of new N-alky- and N-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and Rhesus monkey models. New compounds are generally metabolically stable, weakly active in vitro against Plasmodium falciparum clones (D6 and W2) and in mice infected with Plasmodium berghei sporozoites. Representative compounds 8e and 9c showed good causal prophylactic activity in Rhesus monkeys dosed 30 mg/kg/day for 3 consecutive days by IM, delayed patency for 19-21 days and 54-86 days, respectively, as compared to the untreated control. By oral, 9c showed only marginal activity in causal prophylactic and radical curative tests at 50 mg/kg/day x 3 and 30 mg/kg/day x 7 plus chloroquine 10 mg/kg for 7 days, respectively.

  18. High-sensitivity cardiac troponin testing in routine practice: economic and organizational advantages

    Science.gov (United States)

    Lippi, Giuseppe

    2016-01-01

    Very seldom, if ever, a single laboratory test has provided such a paradigm shift in the managed care as cardiac troponin (cTn) testing. More than twenty years of improvements in test design and analytical features have contributed to revolutionize the clinical recommendations and guidelines, and the diagnosis of myocardial infarction (MI) is now highly dependent upon the kinetics of cTn within a suggestive clinical setting. Despite the advent of high-sensitivity cTn (HS-cTn) immunoassays has allowed a more accurate and timely diagnosis as well as a higher prognostic accuracy, the focus is now shifting on the most suitable algorithms and on a comprehensive approach to the clinical management of acute coronary syndrome (ACS). In this article we aim to discuss the implications of HS-cTn testing for ruling out and ruling in ACS. In the latter instance, main improvements are related to ACS diagnosis in women, in whom this pathology is still often underdiagnosed or misdiagnosed. A quick and accurate rule out will also regarded as a great advantage from both an organizational and economic standpoint. The advantages that will stem from this new approach have been recently assessed, and shortening of repeated testing 1 or 2 h from conventional algorithms entailing blood sampling at 3 and 6 h seems attainable. The larger benefits will definitely occur in clinical settings where the actual diagnosis rate of MI among patients with suspect ACS is lower and, consequently, the negative predictive value (NPV) of HS-cTn is the highest. PMID:27500158

  19. Ligand based validated comparative chemometric modeling and pharmacophore mapping of aurone derivatives as antimalarial agents.

    Science.gov (United States)

    Adhikari, Nilanjan; Halder, Amit Kumar; Mondal, Chanchal; Jha, Tarun

    2013-09-01

    Chloroquine resistance is nowadays a great problem. Aurone derivatives are effective against chloroquine resistant parasite. Ligand based validated comparative chemometric modeling through 2D-QSAR and kNN-MFA 3DQSAR studies as well as common feature 3D pharmacophore mapping were done on thirtyfive aurone derivatives having antimalarial activity. Statistically significant 2D-QSAR models were generated on unsplitted as well as splitted dataset by MLR and PLS technique. The MLR model of the unsplitted method was validated by two-deep cross validation and 10 fold cross validation for determining the predictive ability. The PLS technique of the unsplitted method was done to compare the significance of these methods. In the splitted method, model was developed on the training set by Y-based ranking method by using the same descriptors and was validated on fifty pairs of the test and the training sets by k-MCA technique. These models generated by using the same descriptors were well validated irrespective of MLR as well as PLS analysis of unsplitted as well as splitted methods and are showing similar results. Therefore, these descriptors and model generated were reliable and robust. The kNN-MFA 3D-QSAR models were generated by three variable selection methods: genetic algorithm, simulated annealing and stepwise regression. The kNN-MFA 3D-QSAR results support the 2D QSAR data and in turn validate the earlier observed SAR results. Common feature 3D-pharmacophore generation was performed on these compounds to validate both 2D and 3D-QSAR studies as well as the earlier observed SAR data. The work highlights the required structural features for the higher antimalarial activity. PMID:24010937

  20. Sensitivity analysis of ROSA-III test RUN 704 using RELAP4J code

    International Nuclear Information System (INIS)

    The ROSA-III test RUN 704 is a standard BWR LOCA test, simulating a doublended break in the recirculation pump inlet pipe with the whole emergency core cooling system activation. RELAP4J is a computer code developed to analyze thermal-hydraulic phenomena during a loss of coolant accident, assuming homogeneous equilibrium two-phase model. Sensitivity analysis using RELAP4J code has been done for the test RUN 704. Transient system pressure and boiling transition times are strongly dependent upon the reverse flow form loss coefficient at the jet pump suction. Analysis of quenching precess at the heater surface by the mixture level rise based on the simple phase separation model calculation is by no means easy. Simulations of increase of core inlet flow and core mixture level due to lower plenum flashing are necessary to analyze the rewetting process at the heater surface. There is a strong correlation between mixture level transient in the core and the heater surface temperature transient. An accurate calculation of the heater surface temperature requires an accurate calculation of the core mixture level. The RELAP4J code has to be improved to take into account the counter current flow limiting at both inlet and outlet side of the core and the slip between vapor and liquid in order to calculate the core mixture level transient accurately. (author)

  1. Icosahedral Shallow Water Model (ICOSWM: results of shallow water test cases and sensitivity to model parameters

    Directory of Open Access Journals (Sweden)

    T. Heinze

    2009-06-01

    Full Text Available The Icosahedral Shallow Water Model (ICOSWM has been a first step in the development of the ICON (acronym for ICOsahedral Nonhydrostatic models. ICON is a joint project of the Max Planck Institute for Meteorology in Hamburg (MPI-M and Deutscher Wetterdienst (DWD for the development of new unified general circulation models for climate modeling and numerical weather forecasting on global or regional domains. A short description of ICOSWM is given. Standard test cases are used to test the performance of ICOSWM. The National Center for Atmospheric Research (NCAR Spectral Transform Shallow Water Model (STSWM has been used as reference for test cases without an analytical solution. The sensitivity of the model results to different model parameters is studied. The kinetic energy spectra are calculated and compared to the STSWM spectra. A comparison to the shallow water version of the current operational model GME at DWD is presented. In the framework of the ICON project an hydrostatic dynamical core has been developed, and a local grid refinement option and a non-hydrostatic dynamical core are under development. The results presented in this paper use the ICOSWM version at the end of 2008 and are a benchmark for the new options implemented in the development of these models.

  2. Sensitivity Test of RIA in 5MW Research Reactor during Startup

    International Nuclear Information System (INIS)

    During startup operation, control absorber rods are not located in the equal critical position since they can be manually controlled by an operator without position limitation. Therefore, the power peaking factor in this control mode becomes larger due to the skewed power shape, making the accident consequence worse. In research reactor, the reactor protection system (RPS) has linear power trip and power lograte trip for a safe shutdown of reactor in the accident, and the occurrence of those trips depend both on the initial reactor power and the reactivity insertion rate. Therefore, with a series of sensitive analyses, we identified the most severe combination of initial conditions among the various initial reactor powers and reactivity insertion rates. The model reactor in this analysis is a 5MW pooltype research reactor having two different operation modes; a power operation and a training operation.. Since the accident occurs during startup of the reactor, the training mode without a forced convection results in more severe consequences in a view of fuel integrity. Therefore, the inadvertent withdrawal of a control rod during a startup of training operation is analyzed as a limiting case of the accident. Sensitivity tests with combinations of different initial reactor powers and reactivity insertion rates are performed for an inadvertent CAR withdrawal during startup of the training operation

  3. Identification of lung cancer with high sensitivity and specificity by blood testing

    Directory of Open Access Journals (Sweden)

    Stephan Bernhard

    2010-02-01

    Full Text Available Abstract Background Lung cancer is a very frequent and lethal tumor with an identifiable risk population. Cytological analysis and chest X-ray failed to reduce mortality, and CT screenings are still controversially discussed. Recent studies provided first evidence for the potential usefulness of autoantigens as markers for lung cancer. Methods We used extended panels of arrayed antigens and determined autoantibody signatures of sera from patients with different kinds of lung cancer, different common non-tumor lung pathologies, and controls without any lung disease by a newly developed computer aided image analysis procedure. The resulting signatures were classified using linear kernel Support Vector Machines and 10-fold cross-validation. Results The novel approach allowed for discriminating lung cancer patients from controls without any lung disease with a specificity of 97.0%, a sensitivity of 97.9%, and an accuracy of 97.6%. The classification of stage IA/IB tumors and controls yielded a specificity of 97.6%, a sensitivity of 75.9%, and an accuracy of 92.9%. The discrimination of lung cancer patients from patients with non-tumor lung pathologies reached an accuracy of 88.5%. Conclusion We were able to separate lung cancer patients from subjects without any lung disease with high accuracy. Furthermore, lung cancer patients could be seprated from patients with other non-tumor lung diseases. These results provide clear evidence that blood-based tests open new avenues for the early diagnosis of lung cancer.

  4. Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

    OpenAIRE

    Travers Dominique; Amalvict Rémy; Baret Eric; Basco Leonardo K; Pascual Aurélie; Rogier Christophe; Pradines Bruno

    2011-01-01

    Abstract Background The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods The susceptibility of 36 pre-identified parasite strains from a...

  5. Derivative-based global sensitivity measures: general links with Sobol' indices and numerical tests

    CERN Document Server

    Matieyendou, Matieyendou; Popelin, Anne-Laure; Gamboa, Fabrice

    2012-01-01

    The estimation of variance-based importance measures (called Sobol' indices) of the input variables of a numerical model can require a large number of model evaluations. It turns to be unacceptable for huge model involving a large number of input variables (typically more than ten). Recently, Sobol and Kucherenko have proposed the Derivative-based Global Sensitivity Measures (DGSM), defined as the integral of the squared derivatives of the model output, showing that it can help to solve the problem of dimensionality in some cases. We provide a general inequality link between DGSM and total Sobol' indices for input variables belonging in the class of Boltzmann probability measures, extending the previous results of Sobol and Kucherenko for uniform and normal measures. The special case of log-concave measures is also described. This link provides a DGSM-based maximal bound for the total Sobol indices. Numerical tests show the performance of the bound and its usefulness in practice.

  6. Limits of radiographic testing. New high contrast sensitivity technique - examples and analysis by system theory

    International Nuclear Information System (INIS)

    During the last years more and more reports about film replacement techniques are published using different ways to prove the required and obtained image quality. The motivation is usually cost reduction due to shorter exposure times and lower storage costs, smaller space requirements and elimination of chemical processing inclusive associated waste handling and disposal. New calibration and measurement procedures have been developed to explore the upper limits of image quality (signal-to-noise ratio SNR) achievable with the new digital detector arrays (DDAs). The developed algorithms realize a new high contrast sensitivity technique, which allows distinguishing wall thickness changes down to 1/1000 of the penetrated material thickness. Standard film radiography using the best NDT film systems (class ''C1'' according to EN 584-1) achieves a wall thickness contrast which is limited to 1/100 of the penetrated material thickness. The achieved image qualities of film and DDAs are compared on the basis of a test weldment. (orig.)

  7. High sensitivity tests of the Pauli Exclusion Principle with VIP2

    CERN Document Server

    Marton, J; Bertolucci, S; Berucci, C; Bragadireanu, M; Cargnelli, M; Curceanu, C; Clozza, A; Di Matteo, S; Egger, J-P; Guaraldo, C; Iliescu, M; Ishiwatari, T; Laubenstein, M; Milotti, E; Pichler, A; Pietreanu, D; Piscicchia, K; Ponta, T; Scordo, A; Shi, H; Sirghi, D L; Sirghi, F; Sperandio, L; Doce, O Vazquez; Widmann, E; Zmeskal, J

    2015-01-01

    The Pauli Exclusion Principle is one of the most fundamental rules of nature and represents a pillar of modern physics. According to many observations the Pauli Exclusion Principle must be extremely well fulfilled. Nevertheless, numerous experimental investigations were performed to search for a small violation of this principle. The VIP experiment at the Gran Sasso underground laboratory searched for Pauli-forbidden X-ray transitions in copper atoms using the Ramberg-Snow method and obtained the best limit so far. The follow-up experiment VIP2 is designed to reach even higher sensitivity. It aims to improve the limit by VIP by orders of magnitude. The experimental method, comparison of different PEP tests based on different assumptions and the developments for VIP2 are presented.

  8. High sensitivity tests of the Pauli Exclusion Principle with VIP2

    Science.gov (United States)

    Marton, J.; Bartalucci, S.; Bertolucci, S.; Berucci, C.; Bragadireanu, M.; Cargnelli, M.; Curceanu, C.; Clozza, A.; Di Matteo, S.; Egger, J.-P.; Guaraldo, C.; Iliescu, M.; Ishiwatari, T.; Laubenstein, M.; Milotti, E.; Pichler, A.; Pietreanu, D.; Piscicchia, K.; Ponta, T.; Scordo, A.; Shi, H.; Sirghi, D. L.; Sirghi, F.; Sperandio, L.; Vazquez Doce, O.; Widmann, E.; Zmeskal, J.

    2015-07-01

    The Pauli Exclusion Principle is one of the most fundamental rules of nature and represents a pillar of modern physics. According to many observations the Pauli Exclusion Principle must be extremely well fulfilled. Nevertheless, numerous experimental investigations were performed to search for a small violation of this principle. The VIP experiment at the Gran Sasso underground laboratory searched for Pauli-forbidden X-ray transitions in copper atoms using the Ramberg-Snow method and obtained the best limit so far. The follow-up experiment VIP2 is designed to reach even higher sensitivity. It aims to improve the limit by VIP by orders of magnitude. The experimental method, comparison of different PEP tests based on different assumptions and the developments for VIP2 are presented.

  9. Modal test/analysis correlation of Space Station structures using nonlinear sensitivity

    Science.gov (United States)

    Gupta, Viney K.; Newell, James F.; Berke, Laszlo; Armand, Sasan

    1992-09-01

    The modal correlation problem is formulated as a constrained optimization problem for validation of finite element models (FEM's). For large-scale structural applications, a pragmatic procedure for substructuring, model verification, and system integration is described to achieve effective modal correlation. The space station substructure FEM's are reduced using Lanczos vectors and integrated into a system FEM using Craig-Bampton component modal synthesis. The optimization code is interfaced with MSC/NASTRAN to solve the problem of modal test/analysis correlation; that is, the problem of validating FEM's for launch and on-orbit coupled loads analysis against experimentally observed frequencies and mode shapes. An iterative perturbation algorithm is derived and implemented to update nonlinear sensitivity (derivatives of eigenvalues and eigenvectors) during optimizer iterations, which reduced the number of finite element analyses.

  10. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna Chaijaroenkul; Artitiya Thiengsusuk; Kanchana Rungsihirunrat; Stephen Andrew Ward; Kesara Na-Bangchang

    2014-01-01

    Objective: To investigate possible protein targets for antimalarial activity of Garcinia mangostana Linn. (G. mangostana) (pericarp) in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry (LC/MS/MS). Methods: 3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn. (pericarp) at the concentrations of 12µg/mL (IC50 level: concentration that inhibits parasite growth by 50%) and 30 µg/mL (IC90 level: concentration that inhibits parasite growth by 90%) for 12 h. Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50 concentration, about 82% of the expressed parasite proteins were matched with the control (non-exposed), while at the IC90 concentration, only 15% matched proteins were found. The selected protein spots from parasite exposed to the plant extract at the concentration of 12 µg/mL were identified as enzymes that play role in glycolysis pathway, i.e., phosphoglycerate mutase putative, L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase, and fructose-bisphosphate aldolase/phosphoglycerate kinase. The proteosome was found in parasite exposed to 30 µg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G. mangostana Linn. (pericarp).

  11. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna; Chaijaroenkul; Artitiya; Thiengsusuk; Kanchana; Rungsihirunrat; Stephen; Andrew; Ward; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate possible protein targets for antimalarial activity of Garcina mangostana Linn.(G.mangostana)(pericarp)in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry(LC/MS/MS).Methods:3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn.(pericarp)at the concentrations of 12μg/mL(1C50level:concentration that inhibits parasite growth by 50%)and 30μg/mL(1C90level:concentration that inhibits parasite growth by 90%)for 12 h.Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50concentration,about 82%of the expressed parasite proteins were matched with the control(non-exposed),while at the IC90concentration,only 15%matched proteins were found.The selected protein spots from parasite exposed to the plant extract at the concentration of 12μg/mL were identified as eneymes that play role in glycolysis pathway,i.e.,phosphoglyeerate mutase putative,L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase,and fruetose-bisphosphate aldolase/phosphoglyeerate kinase.The proteosome was found in parasite exposed to 30μg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G.mangostana Linn.(pericarp).

  12. Fake anti-malarials: start with the facts.

    Science.gov (United States)

    Kaur, Harparkash; Clarke, Siȃn; Lalani, Mirza; Phanouvong, Souly; Guérin, Philippe; McLoughlin, Andrew; Wilson, Benjamin K; Deats, Michael; Plançon, Aline; Hopkins, Heidi; Miranda, Debora; Schellenberg, David

    2016-01-01

    This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting. PMID:26873700

  13. Antimalarials and the fight against malaria in Brazil.

    Science.gov (United States)

    Carmargo, Luiz Ma; de Oliveira, Saulo; Basano, Sergio; Garcia, Célia Rs

    2009-08-01

    Malaria, known as the "fevers," has been treated for over three thousand years in China with extracts of plants of the genus Artemisia (including Artemisia annua, A. opiacea, and A. lancea) from which the active compound is artemisin, a sesquiterpene that is highly effective in the treatment of the disease, especially against young forms of the parasite. South American Indians in the seventeenth century already used an extract of the bark of chinchona tree, commonly named "Jesuits' powder." Its active compound was isolated in 1820 and its use spread all over the world being used as a prophylactic drug during the construction of the Madeira-Mamoré railroad in the beginning of the twentieth century. During the 1920s to the 1940s, new antimalarial drugs were synthesized to increase the arsenal against this parasite. However, the parasite has presented systematic resistence to conventional antimalarial drugs, driving researchers to find new strategies to treat the disease. In the present review we discuss how Brazil treats Plasmodium-infected patients. PMID:19753125

  14. Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

    Directory of Open Access Journals (Sweden)

    Kaludov Nikola

    2011-09-01

    Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a

  15. Malaria: Antimalarial resistance and policy ramificationsand challenges

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2006-01-01

    Full Text Available ′The National health Policy 2002" of India and the "Roll Back Malaria" policy makers have set up an ambitious goal of reducing malaria mortality and morbidity by 25% by 2007, and by 50% by 2010. To achieve these goals, problems should be identified, available evidence analyzed and policy should be changed early. Infection with drug resistant malarial parasites has a tremendous impact on health (prolonged recurrent illness, increased hospital admissions and death, health system (higher cost of treatment and socioeconomics of the region. In view of the evidence of the economic burden of malaria, it has been suggested that second line treatment could be considered at 10% failure instead of 25%. Effective schizonticidal drugs will not only reduce morbidity and mortality but will also reduce transmission. Studies have shown that prevalence of viable (as tested by exflagellation test gametocytes is considerably more after the Chloroquine or Chloroquine + Sulphadoxine-Pyrimethamine treatment compared to Quinine. Unfortunately, the only gametocytocidal drug for Plasmodium falciparum, primaquine, is also loosing its efficacy. 45 mg Primaquine reduces gametocyte prevalence by 50% while a new drug, 75 mg bulaquine or 60 mg primaquine reduces it by 90%. Plasmodium vivax forms 60-70% of malaria cases in India. Relapses which occur in 10-20% of cases adds to the burden. Efficacy, as confirmed by Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCRSSCP to differentiate relapse and re-infection, of standard dose of primaquine (15 mg/day for 5 days, even 15 mg/day for 14 days for vivax malaria is reducing. Fourteen day treatment is also impractical as compliance is poor. Newer drugs, newer drug delivery systems are thus needed. Slow release formulations with blood levels maintained for one week may be useful. Rationale of giving primaquine in higher doses and different timing need to be considered. The genome of Plasmodium falciparum and

  16. An extremely sensitive species-specific ARMS PCR test for the presence of tiger bone DNA.

    Science.gov (United States)

    Wetton, Jon H; Tsang, Carol S F; Roney, Chris A; Spriggs, Adrian C

    2002-04-18

    The survival of the tiger (Panthera tigris) is seriously threatened by poaching to provide raw materials for traditional Chinese medicines (TCMs). Most highly prized are the tiger's bones, which are used in combination with other animal and plant derivatives in pills and plasters for the treatment of rheumatism and other ailments. Hundreds of patent remedies have been produced which claim to contain tiger bone, but proof of its presence is needed if legislation prohibiting the trade in endangered species is to be enforced.A highly sensitive tiger-specific real-time PCR assay has been developed to address this problem. Using primers specific to the tiger mitochondrial cytochrome b gene, successful amplification has been reliably achieved from blood, hair and bone as well as from a range of TCMs spiked with 0.5% tiger bone. Although capable of detecting fewer than 10 substrate molecules, the seven varieties of TCM pills and plasters tested showed no detectable trace of tiger DNA before spiking. Furthermore, sequencing several "tiger bone" fragments seized from TCM shops has shown that they actually originated from cattle and pigs. The potential effects of traditional bone preparation methods, evidence that much lower concentrations are used than alleged on TCM packaging, and substitution of bones from other species all suggest a low likelihood of detecting tiger DNA in patent medicines. Despite this, the basic methods have been thoroughly proven and can be readily applied to derivatives from other Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) protected species, providing a rapid and highly sensitive forensic test for species of origin. Potential applications to the monitoring of wild populations are demonstrated by the successful identification of shed hairs and faecal samples. PMID:12084490

  17. Specificity, sensitivity, and reproducibility among the fluorescent treponemal antibody-absorption test, the microhemagglutination assay for Treponema pallidum antibodies, and the hemagglutination treponemal test for syphilis.

    OpenAIRE

    Larsen, S A; Hambie, E A; Pettit, D E; Perryman, M W; Kraus, S J

    1981-01-01

    Using 920 sera, we compared the specificity and reproducibility of the hemagglutination treponemal test for syphilis with those of the fluorescent treponemal antibody-absorption test and the microhemagglutination assay for Treponema pallidum antibodies; we found all three tests to be comparable. However, the hemagglutination treponemal test for syphilis, like the microhemagglutination assay for T. pallidum antibodies, lacked sensitivity in sera from patients with primary syphilis.

  18. A short-term in vitro test for tumour sensitivity to adriamycin based on flow cytometric DNA analysis

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1983-01-01

    A new method to test the sensitivity of tumour cells to chemotherapy is presented. Tumour cells were incubated in vitro on agar, and drug-induced cell cycle perturbation was monitored by flow cytometric DNA analysis. In the present study the method was applied to monitor the effect of adriamycin on...... resistant tumours. The dose level causing maximum accumulation in the G2 + M phase is suggested as a parameter for quantifying the sensitivity. The results indicate that the method can be extended to sensitivity testing of human tumours....

  19. Distillation Time as Tool for Improved Antimalarial Activity and Differential Oil Composition of Cumin Seed Oil.

    Science.gov (United States)

    Zheljazkov, Valtcho D; Gawde, Archana; Cantrell, Charles L; Astatkie, Tess; Schlegel, Vicki

    2015-01-01

    A steam distillation extraction kinetics experiment was conducted to estimate essential oil yield, composition, antimalarial, and antioxidant capacity of cumin (Cuminum cyminum L.) seed (fruits). Furthermore, regression models were developed to predict essential oil yield and composition for a given duration of the steam distillation time (DT). Ten DT durations were tested in this study: 5, 7.5, 15, 30, 60, 120, 240, 360, 480, and 600 min. Oil yields increased with an increase in the DT. Maximum oil yield (content, 2.3 g/100 seed), was achieved at 480 min; longer DT did not increase oil yields. The concentrations of the major oil constituents α-pinene (0.14-0.5% concentration range), β-pinene (3.7-10.3% range), γ-cymene (5-7.3% range), γ-terpinene (1.8-7.2% range), cumin aldehyde (50-66% range), α-terpinen-7-al (3.8-16% range), and β-terpinen-7-al (12-20% range) varied as a function of the DT. The concentrations of α-pinene, β-pinene, γ-cymene, γ-terpinene in the oil increased with the increase of the duration of the DT; α-pinene was highest in the oil obtained at 600 min DT, β-pinene and γ-terpinene reached maximum concentrations in the oil at 360 min DT; γ-cymene reached a maximum in the oil at 60 min DT, cumin aldehyde was high in the oils obtained at 5-60 min DT, and low in the oils obtained at 240-600 min DT, α-terpinen-7-al reached maximum in the oils obtained at 480 or 600 min DT, whereas β-terpinen-7-al reached a maximum concentration in the oil at 60 min DT. The yield of individual oil constituents (calculated from the oil yields and the concentration of a given compound at a particular DT) increased and reached a maximum at 480 or 600 min DT. The antimalarial activity of the cumin seed oil obtained during the 0-5 and at 5-7.5 min DT timeframes was twice higher than the antimalarial activity of the oils obtained at the other DT. This study opens the possibility for distinct marketing and utilization for these improved oils. The antioxidant

  20. Phytochemical screening and in vivo antimalarial activity of extracts from three medicinal plants used in malaria treatment in Nigeria.

    Science.gov (United States)

    Bankole, A E; Adekunle, A A; Sowemimo, A A; Umebese, C E; Abiodun, O; Gbotosho, G O

    2016-01-01

    The use of plant to meet health-care needs has greatly increased worldwide in the recent times. The search for new plant-derived bioactive agents that can be explored for the treatment of drug-resistant malaria infection is urgently needed. Thus, we evaluated the antimalarial activity of three medicinal plants used in Nigerian folklore for the treatment of malaria infection. A modified Peter's 4-day suppressive test was used to evaluate the antimalarial activity of the plant extracts in a mouse model of chloroquine-resistant Plasmodium berghei ANKA strain. Animals were treated with 250, 500, or 800 mg/kg of aqueous extract. It was observed that of all the three plants studied, Markhamia tomentosa showed the highest chemosuppression of parasites of 73 % followed by Polyalthia longifolia (53 %) at day 4. All the doses tested were well tolerated. Percentage suppression of parasite growth on day 4 post-infection ranged from 1 to 73 % in mice infected with P. berghei and treated with extracts when compared with chloroquine diphosphate, the standard reference drug which had a chemosuppression of 90 %. The percentage survival of mice that received extract ranged from 0 to 60 % (increased as the dose increases to 800 mg/kg). Phytochemical analysis revealed the presence of tannins, saponins, and phenolic compounds in all the three plants tested. PMID:26391173

  1. Comparison of the Exposure Time Dependence of the Activities of Synthetic Ozonide Antimalarials and Dihydroartemisinin against K13 Wild-Type and Mutant Plasmodium falciparum Strains

    Science.gov (United States)

    Yang, Tuo; Xie, Stanley C.; Cao, Pengxing; Giannangelo, Carlo; McCaw, James; Creek, Darren J.; Charman, Susan A.; Klonis, Nectarios

    2016-01-01

    Fully synthetic endoperoxide antimalarials, namely, OZ277 (RBx11160; also known as arterolane) and OZ439 (artefenomel), have been approved for marketing or are currently in clinical development. We undertook an analysis of the kinetics of the in vitro responses of Plasmodium falciparum to the new ozonide antimalarials. For these studies we used a K13 mutant (artemisinin resistant) isolate from a region in Cambodia and a genetically matched (artemisinin sensitive) K13 revertant. We used a pulsed-exposure assay format to interrogate the time dependence of the response. Because the ozonides have physicochemical properties different from those of the artemisinins, assay optimization was required to ensure that the drugs were completely removed following the pulsed exposure. Like that of artemisinins, ozonide activity requires active hemoglobin degradation. Short pulses of the ozonides were less effective than short pulses of dihydroartemisinin; however, when early-ring-stage parasites were exposed to drugs for periods relevant to their in vivo exposure, the ozonide antimalarials were markedly more effective. PMID:27161632

  2. A combination of the leaves and tuber ofIcacina senegalensis A. Juss (Icacinaceae) improves the antimalarial activity of the plant in mice

    Institute of Scientific and Technical Information of China (English)

    Esien David-Oku; Juliet Ifeoma Obiajunwa-Otteh

    2015-01-01

    Objective:To investigate the possibility of increased antimalarial activity ofIcacina senegalensis A. Juss (Icacinaceae) upon a combination of its leaves and tubers against Plasmodium berghei malaria in mice. Methods: Chloroquine sensitiveANKA clones ofPlasmodium berghei were used to develop experimental models based on intraperitoneal injection of 107 parasitized erythrocytes in phosphate buffer saline (pH 7.2) and subsequent development of parasitemia. The models were employed to investigate prophylactic and curative anti-malarial activities of tuber and tuber-leaf methanol extracts of the plant at selected dosages (25, 50 and 100 mg/kg body weight). Chloroquine with a curative dosage of 10 mg/kg body weight was used as positive control in both studies. Results:Tuber and tuber-leaf extracts produced a dose-dependent chemosuppression of the parasites, with higher activity and mean survival time exhibited by the combined extract. Conclusions:Anti-plasmodia activity has been discovered in methanol extract ofIcacina senegalensis tuber extract. The observed optimization of the antimalarial actions of the plant upon a combination of its leaf and tuber opens a new area of medicinal plant research.

  3. Lagrangian model of zooplankton dispersion: numerical schemes comparisons and parameter sensitivity tests

    Institute of Scientific and Technical Information of China (English)

    QIU Zhongfeng; Andrea M. DOGLIOLI; HE Yijun; Francois CARLOTTI

    2011-01-01

    This paper presents two comparisons or tests for a Lagrangian model of zooplankton dispersion: numerical schemes and time steps. Firstly, we compared three numerical schemes using idealized circulations. Results show that the precisions of the advanced Adams-Bashfold-Moulton (ABM) method and the Runge-Kutta (RK) method were in the same order and both were much higher than that of the Euler method. Furthermore, the advanced ABM method is more efficient than the RK method in computational memory requirements and time consumption. We therefore chose the advanced ABM method as the Lagrangian particle-tracking algorithm. Secondly, we performed a sensitivity test for time steps, using outputs of the hydrodynamic model, Symphonie. Results show that the time step choices depend on the fluid response time that is related to the spatial resolution of velocity fields. The method introduced by Oliveira et al. in 2002 is suitable for choosing time steps of Lagrangian particle-tracking models, at least when only considering advection.

  4. A relay strategy for the mercury (II) chemodosimeter with ultra-sensitivity as test strips

    Science.gov (United States)

    Ruan, Zhijun; Li, Conggang; Li, Jian-Rong; Qin, Jingui; Li, Zhen

    2015-11-01

    A relay strategy has been proposed to design a new Hg2+ chemodosimeter (TPE-S), by coupling Hg2+-promoted deprotection reaction with ketone-enol isomerization, realizing the multistage amplifying effect. Changes in both of color and fluorescence could occur immediately, and TPE-S displayed high selectivity for Hg2+, other metal ions (Ag+, Fe3+, Cu2+, Pb2+, Co2+, Cr3+, Al3+, Cd2+, Mg2+, Mn2+, Ba2+, Fe2+, Ca2+, Ni2+, Zn2+, Li+, K+ and Na+) gave nearly no disturbance to the sensing process. When fabricated as test strips similar to pH-indicator papers, immediate color change from colorless to purple could be visually observed by naked-eyes without the aid of any additional equipment, with the detection limit as low as 1 × 10-7 M (Hg2+ in aqueous solution). Due to its easy synthesis, high selectivity and sensitivity, combined with the portable test strips, TPE-S could be developed as a convenient and cost-effective tool for the detection of Hg2+ in on-site inspections.

  5. Rapid and sensitive loop-mediated isothermal amplification test for Clostridium difficile detection challenges cytotoxin B cell test and culture as gold standard.

    Science.gov (United States)

    Norén, Torbjörn; Alriksson, Ingegärd; Andersson, Josefin; Akerlund, Thomas; Unemo, Magnus

    2011-02-01

    Compared to the composite gold standard cytotoxin B assay and toxigenic culture, the loop-mediated isothermal amplification (LAMP) test for Clostridium difficile had a sensitivity and specificity of 98%, positive predictive value of 92%, and negative predictive value of >99%. A one-hour turnaround time for the LAMP test provides rapid diagnosis and cost savings. PMID:21106782

  6. Rapid and Sensitive Loop-Mediated Isothermal Amplification Test for Clostridium difficile Detection Challenges Cytotoxin B Cell Test and Culture as Gold Standard▿

    OpenAIRE

    Norén, Torbjörn; Alriksson, Ingegärd; Andersson, Josefin; Åkerlund, Thomas; Unemo, Magnus

    2011-01-01

    Compared to the composite gold standard cytotoxin B assay and toxigenic culture, the loop-mediated isothermal amplification (LAMP) test for Clostridium difficile had a sensitivity and specificity of 98%, positive predictive value of 92%, and negative predictive value of >99%. A one-hour turnaround time for the LAMP test provides rapid diagnosis and cost savings.

  7. Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

    Directory of Open Access Journals (Sweden)

    Humberto Andres Vaz

    2016-04-01

    Full Text Available Abstract Background: The kinetics of high-sensitivity troponin T (hscTnT release should be studied in different situations, including functional tests with transient ischemic abnormalities. Objective: To evaluate the release of hscTnT by serial measurements after exercise testing (ET, and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Methods: Patients with acute ST-segment elevation myocardial infarction (STEMI undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT0h, 2 (TnT2h, 5 (TnT5h, and 8 hours (TnT8h after ET. The outcomes were peak hscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT0h, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance. Results: This study included 95 patients. The highest geometric means were observed at 5 hours (TnT5h. After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002, 59% (p = 0.003 and 45% (p = 0.003 higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Conclusion: Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI.

  8. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Cortinas, Inés Vidal, E-mail: invi@montevideo.com.uy; Beretta, Mario; Alonso, Omar; Mut, Fernando [Departamento de Medicina Nuclear do Hospital ‘Asociación Española’, Br. Artigas 1515, Montevideo (Uruguay)

    2015-08-15

    Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  9. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Directory of Open Access Journals (Sweden)

    Inés Vidal Cortinas

    2015-08-01

    Full Text Available AbstractBackground:Myocardial perfusion scintigraphy (MPS in patients not reaching 85% of the maximum predicted heart rate (MPHR has reduced sensitivity.Objectives:In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols.Methods:In patients not reaching a sufficient exercise (SE test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection.Results:Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR and 67 underwent the dipyridamole alone test (DIP. They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43. For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35. Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001.Conclusions:The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  10. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    International Nuclear Information System (INIS)

    Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP

  11. Use of a radiorespirometric assay for testing the antibiotic sensitivity of catheter-associated bacteria

    International Nuclear Information System (INIS)

    A 14C-radiorespirometric assay was used to show the sensitivity of fixed-film (sessile), catheter-associated and free-living (planktonic) cells of Pseudomonas aeruginosa to varying concentrations (100 micrograms/mL to 1000 micrograms/mL) tobramycin sulfate. This strain of P. aeruginosa has an MIC of 0.6 microgram/ml and an MBC of 50 micrograms/mL when tested by conventional methods. When 14C-glutamic acid was used as a substrate in this radiorespirometric assay, it could be completed in less than one hour and planktonic samples showed a significant reduction in mineralization activity (evolution of 14CO2) within eight hours of the antibiotic challenge. These changes in respiratory activity appeared to be dose and time dependent. Within 18 hr. at 1000 micrograms/mL, there was no significant residual respiratory activity in planktonic samples. Some residual respiratory activity was detected, however, in samples exposed to 100 micrograms/mL for 36 hours. The mineralization activity of sessile catheter-associated bacteria was unaffected by four hr. and eight hr. exposures to 1000 micrograms/mL of the antibiotic. A significant reduction in respiratory activity was recorded in catheter samples exposed for 18 hr. or more at each concentration examined. Unlike the planktonic samples, however, the antibiotic challenge failed to eradicate the metabolic activity of the attached bacteria. Antibiotic stressed, catheter-associated bacteria transferred to a post-exposure enrichment broth showed a limited ability to re-establish respiratory activity. This apparent recovery was limited to antibiotic exposures less than 24 hr. and was not observed in planktonic samples. The radioisotopic assay is a non-culture method which can be used to assess the antibiotic sensitivity of both planktonic bacteria and in situ biofilm populations

  12. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Directory of Open Access Journals (Sweden)

    Albrekt Ann-Sofie

    2011-08-01

    Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

  13. Gas migration in KBS-3 buffer bentonite. Sensitivity of test parameters to experimental boundary conditions

    International Nuclear Information System (INIS)

    In the current Swedish repository design concept, hydrogen gas can be generated inside a waste canister by anaerobic corrosion of the ferrous metal liner. If the gas generation rate exceeds the diffusion rate of gas molecules in the buffer porewater, gas will accumulate in the void-space of a canister until its pressure becomes large enough for it to enter the bentonite as a discrete gaseous phase. Three long tenn gas injection tests have been performed on cylinders of pre-compacted MX80 bentonite. Two of these tests were undertaken using a custom-designed constant volume and radial flow (CVRF) apparatus. Gas was injected at a centrally located porous filter installed in the clay before hydration. Arrangements were made for gas to flow to three independently monitored sink-filter arrays mounted around the specimen. Axial and radial total stresses and internal porewater pressures were continuously monitored. Breakthrough and peak gas pressures were substantially larger than the sum of the swelling pressure and the external porewater. The third test was performed. using an apparatus which radially constrains the specimen during gas flow. Observed sensitivity of the breakthrough and peak gas pressures to the test boundary conditions suggests that gas entry must be accompanied by dilation of the bentonite fabric. In other words, there is a tendency for the volume of the specimen to increase during this process. The experimental evidence is consistent with the flow of gas along a relatively small number of crack-like pathways which propagate through the clay as gas pressure increases. Gas entry and breakthrough under constant volume boundary conditions causes a substantial increase in the total stress and the internal porewater pressure. It is possible to determine the point at which gas enters the clay by monitoring changes in these parameters. Localisation of gas flow within multiple pathways results, in nonuniform discharge rates at the sinks. When gas injection

  14. Sensitivity of wetland methane emissions to model assumptions: application and model testing against site observations

    Directory of Open Access Journals (Sweden)

    L. Meng

    2012-07-01

    Full Text Available Methane emissions from natural wetlands and rice paddies constitute a large proportion of atmospheric methane, but the magnitude and year-to-year variation of these methane sources are still unpredictable. Here we describe and evaluate the integration of a methane biogeochemical model (CLM4Me; Riley et al., 2011 into the Community Land Model 4.0 (CLM4CN in order to better explain spatial and temporal variations in methane emissions. We test new functions for soil pH and redox potential that impact microbial methane production in soils. We also constrain aerenchyma in plants in always-inundated areas in order to better represent wetland vegetation. Satellite inundated fraction is explicitly prescribed in the model, because there are large differences between simulated fractional inundation and satellite observations, and thus we do not use CLM4-simulated hydrology to predict inundated areas. A rice paddy module is also incorporated into the model, where the fraction of land used for rice production is explicitly prescribed. The model is evaluated at the site level with vegetation cover and water table prescribed from measurements. Explicit site level evaluations of simulated methane emissions are quite different than evaluating the grid-cell averaged emissions against available measurements. Using a baseline set of parameter values, our model-estimated average global wetland emissions for the period 1993–2004 were 256 Tg CH4 yr−1 (including the soil sink and rice paddy emissions in the year 2000 were 42 Tg CH4 yr−1. Tropical wetlands contributed 201 Tg CH4 yr−1, or 78% of the global wetland flux. Northern latitude (>50 N systems contributed 12 Tg CH4 yr−1. However, sensitivity studies show a large range (150–346 Tg CH4 yr−1 in predicted global methane emissions (excluding emissions from rice paddies. The large range is

  15. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses

    Directory of Open Access Journals (Sweden)

    Farrar Jeremy

    2010-05-01

    Full Text Available Abstract Background Dengue is a major public health problem in tropical and subtropical countries. Rapid and easy diagnosis of dengue can assist patient triage and care-management. The detection of DENV NS1 on rapid lateral flow tests offers a fast route to a presumptive dengue diagnosis but careful evaluations are urgently needed as more and more people use them. Methods The sensitivity and specificity of the Bio-Rad NS1 Ag Strip and SD Dengue Duo (NS1/IgM/IgG lateral flow rapid tests were evaluated in a panel of plasma samples from 245 Vietnamese patients with RT-PCR confirmed dengue and 47 with other febrile illnesses. Results The NS1 rapid tests had similar diagnostic sensitivities (respectively 61.6% and 62.4% in confirmed dengue cases but were 100% specific. When IgM/IgG results from the SD Dengue Duo were included in the test interpretation, the sensitivity improved significantly from 62.4% with NS1 alone to 75.5% when NS1 and/or IgM was positive and 83.7% when NS1 and/or IgM and/or IgG was positive. Both NS1 assays were significantly more sensitive for primary than secondary dengue. NS1 positivity was associated with the underlying viraemia as NS1-positive samples had a significantly higher viraemia than NS1-negative samples. Conclusions These data suggest that the NS1 test component of these assays are highly specific and have similar levels of sensitivity. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. The SD Dengue Duo lateral flow rapid test deserves further prospective evaluation in dengue endemic settings.

  16. Process Sensitivity, Performance, and Direct Verification Testing of Adhesive Locking Features

    Science.gov (United States)

    Golden, Johnny L.; Leatherwood, Michael D.; Montoya, Michael D.; Kato, Ken A.; Akers, Ed

    2012-01-01

    Phase I: The use of adhesive locking features or liquid locking compounds (LLCs) (e.g., Loctite) as a means of providing a secondary locking feature has been used on NASA programs since the Apollo program. In many cases Loctite was used as a last resort when (a) self-locking fasteners were no longer functioning per their respective drawing specification, (b) access was limited for removal & replacement, or (c) replacement could not be accomplished without severe impact to schedule. Long-term use of Loctite became inevitable in cases where removal and replacement of worn hardware was not cost effective and Loctite was assumed to be fully cured and working. The NASA Engineering & Safety Center (NESC) and United Space Alliance (USA) recognized the need for more extensive testing of Loctite grades to better understand their capabilities and limitations as a secondary locking feature. These tests, identified as Phase I, were designed to identify processing sensitivities, to determine proper cure time, the correct primer to use on aerospace nutplate, insert and bolt materials such as A286 and MP35N, and the minimum amount of Loctite that is required to achieve optimum breakaway torque values. The .1900-32 was the fastener size tested, due to wide usage in the aerospace industry. Three different grades of Loctite were tested. Results indicate that, with proper controls, adhesive locking features can be successfully used in the repair of locking features and should be considered for design. Phase II: Threaded fastening systems used in aerospace programs typically have a requirement for a redundant locking feature. The primary locking method is the fastener preload and the traditional redundant locking feature is a self-locking mechanical device that may include deformed threads, non-metallic inserts, split beam features, or other methods that impede movement between threaded members. The self-locking resistance of traditional locking features can be directly verified

  17. GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe

    DEFF Research Database (Denmark)

    Heinzerling, L M; Burbach, G J; Edenharter, G;

    2009-01-01

    . This could partly be related to changes in mobility of patients, vegetation or climate in Europe. CONCLUSION: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test...... with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed....

  18. Test Sensitivity in the Computer-Aided Detection of Breast Cancer from Clinical Mammographic Screening: a Meta-analysis

    CERN Document Server

    Levman, Jacob

    2013-01-01

    Objectives: To assess evaluative methodologies for comparative measurements of test sensitivity in clinical mammographic screening trials of computer-aided detection (CAD) technologies. Materials and Methods: This meta-analysis was performed by analytically reviewing the relevant literature on the clinical application of computer-aided detection (CAD) technologies as part of a breast cancer screening program based on x-ray mammography. Each clinical study's method for measuring the CAD system's improvement in test sensitivity is examined in this meta-analysis. The impact of the chosen sensitivity measurement on the study's conclusions are analyzed. Results: This meta-analysis demonstrates that some studies have inappropriately compared sensitivity measurements between control groups and CAD enabled groups. The inappropriate comparison of control groups and CAD enabled groups can lead to an underestimation of the benefits of the clinical application of computer-aided detection technologies. Conclusions: The po...

  19. Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials.

    Science.gov (United States)

    Norcross, Neil R; Baragaña, Beatriz; Wilson, Caroline; Hallyburton, Irene; Osuna-Cabello, Maria; Norval, Suzanne; Riley, Jennifer; Stojanovski, Laste; Simeons, Frederick R C; Porzelle, Achim; Grimaldi, Raffaella; Wittlin, Sergio; Duffy, Sandra; Avery, Vicky M; Meister, Stephan; Sanz, Laura; Jiménez-Díaz, Belén; Angulo-Barturen, Iñigo; Ferrer, Santiago; Martínez, María Santos; Gamo, Francisco Javier; Frearson, Julie A; Gray, David W; Fairlamb, Alan H; Winzeler, Elizabeth A; Waterson, David; Campbell, Simon F; Willis, Paul; Read, Kevin D; Gilbert, Ian H

    2016-07-14

    In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting. PMID:27314305

  20. Drug resistance genomics of the antimalarial drug artemisinin.

    Science.gov (United States)

    Winzeler, Elizabeth A; Manary, Micah J

    2014-01-01

    Across the globe, over 200 million annual malaria infections result in up to 660,000 deaths, 77% of which occur in children under the age of five years. Although prevention is important, malaria deaths are typically prevented by using antimalarial drugs that eliminate symptoms and clear parasites from the blood. Artemisinins are one of the few remaining compound classes that can be used to cure multidrug-resistant Plasmodium falciparum infections. Unfortunately, clinical trials from Southeast Asia are showing that artemisinin-based treatments are beginning to lose their effectiveness, adding renewed urgency to the search for the genetic determinants of parasite resistance to this important drug class. We review the genetic and genomic approaches that have led to an improved understanding of artemisinin resistance, including the identification of resistance-conferring mutations in the P. falciparum kelch13 gene. PMID:25470531

  1. Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

    Directory of Open Access Journals (Sweden)

    Laurent Calcul

    2013-12-01

    Full Text Available We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (14–16, 18 were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14, which was found to display the most favorable bioactivity profile.

  2. Triterpenes from Minquartia guianensis (Olacaceae) and in vitro antimalarial activity

    Energy Technology Data Exchange (ETDEWEB)

    Cursino, Lorena Mayara de Carvalho; Nunez, Cecilia Veronica [Instituto Nacional de Pesquisas da Amazonia (INPA), Manaus, AM (Brazil). Lab. de Bioprospeccao e Biotecnologia; Paula, Renata Cristina de; Nascimento, Maria Fernanda Alves do [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Farmacia. Dept. de Produtos Farmaceuticos; Santos, Pierre Alexandre dos, E-mail: cecilia@inpa.gov.br [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil). Fac. de Ciencias Farmaceuticas

    2012-07-01

    Minquartia guianensis, popularly known as acariquara, was phytochemically investigated. The following triterpenes were isolated from the dichloromethane extract of leaves: lupen-3-one (1), taraxer-3-one (2) and oleanolic acid (3). The dichloromethane extract of branches yielded the triterpene 3{beta}-methoxy-lup-20(29)-ene (4). The chemical structures were characterized by NMR data. Plant extracts, substance 3, squalene (5) and taraxerol (6), (5 and 6 previously isolated), were evaluated by in vitro assay against chloroquine resistant Plasmodium falciparum. The dichloromethane extract of leaves and the three triterpenes assayed have shown partial activity. Thus, these results demonstrated that new potential antimalarial natural products can be found even in partially active extracts. (author)

  3. Sensitive immunochemical approaches for quantitative (FPIA) and qualitative (lateral flow tests) determination of gentamicin in milk.

    Science.gov (United States)

    Beloglazova, N V; Shmelin, P S; Eremin, S A

    2016-03-01

    Three kinds of immunoassays for the determination of gentamicin in milk samples were developed and validated. First, a fast and easily-performed fluorescence polarization immunoassay was used for characterization of the employed polyclonal antibody. The calculated Kaff were (1.9±0.4)×10(9)М(-1) and (6.0±0.2)×10(6)М(-1) for the high- and low-affinity fractions respectively. The assay was characterized with a good sensitivity, the limit of detection being 5μgkg(-1). Two different kinds of detection labels, i.e. colloidal gold (CG) and quantum dots (QDs), were evaluated for use in lateral-flow format with respect to rapid visual on-site testing. The cut-off levels for both qualitative formats were selected based on the maximum level for gentamicin in milk established by the European Commission, 100μgkg(-1), resulting in a 10μgkg(-1) cut-off considering sample dilution. The intra-laboratory validation was performed with sterilized milk samples artificially spiked with gentamicin at concentrations less than, equal to, and greater than the cut-off level. It was shown that milk products could be analyzed without any sample preparation, except for dilution with the buffer solution. The rates of false-positive and false-negative results were below 5% for both labels. The different developed immunoassays were tested towards gentamicin determination in artificially-spiked and naturally contaminated milk samples. PMID:26717834

  4. A highly sensitive and simply operated protease sensor toward point-of-care testing.

    Science.gov (United States)

    Park, Seonhwa; Shin, Yu Mi; Seo, Jeongwook; Song, Ji-Joon; Yang, Haesik

    2016-04-21

    Protease sensors for point-of-care testing (POCT) require simple operation, a detection period of less than 20 minutes, and a detection limit of less than 1 ng mL(-1). However, it is difficult to meet these requirements with protease sensors that are based on proteolytic cleavage. This paper reports a highly reproducible protease sensor that allows the sensitive and simple electrochemical detection of the botulinum neurotoxin type E light chain (BoNT/E-LC), which is obtained using (i) low nonspecific adsorption, (ii) high signal-to-background ratio, and (iii) one-step solution treatment. The BoNT/E-LC detection is based on two-step proteolytic cleavage using BoNT/E-LC (endopeptidase) and l-leucine-aminopeptidase (LAP, exopeptidase). Indium-tin oxide (ITO) electrodes are modified partially with reduced graphene oxide (rGO) to increase their electrocatalytic activities. Avidin is then adsorbed on the electrodes to minimize the nonspecific adsorption of proteases. Low nonspecific adsorption allows a highly reproducible sensor response. Electrochemical-chemical (EC) redox cycling involving p-aminophenol (AP) and dithiothreitol (DTT) is performed to obtain a high signal-to-background ratio. After adding a C-terminally AP-labeled oligopeptide, DTT, and LAP simultaneously to a sample solution, no further treatment of the solution is necessary during detection. The detection limits of BoNT/E-LC in phosphate-buffered saline are 0.1 ng mL(-1) for an incubation period of 15 min and 5 fg mL(-1) for an incubation period of 4 h. The detection limit in commercial bottled water is 1 ng mL(-1) for an incubation period of 15 min. The developed sensor is selective to BoNT/E-LC among the four types of BoNTs tested. These results indicate that the protease sensor meets the requirements for POCT. PMID:26980003

  5. Gender differences in sensitivity of acetylcholine and ergonovine to coronary spasm provocation test.

    Science.gov (United States)

    Sueda, Shozo; Miyoshi, Toru; Sasaki, Ysuhiro; Sakaue, Tomoki; Habara, Hirokazu; Kohno, Hiroaki

    2016-03-01

    We examined the sex difference concerning the coronary artery response between ACh and ER in this study. We already reported the difference of coronary response between acetylcholine (ACh) and ergonovine (ER). We performed both ACh and ER tests of 461 patients (male 294 patients, female 167 patients, mean age 64.4 ± 11.3 years) during 23 years. Positive coronary spasm was defined as >99 % transient luminal narrowing with usual chest pain and/or ischemic ECG changes. Firstly, ACh was administered in incremental doses of 20/50/(80) μg into the RCA and 20/50/100/(200) μg into the LCA over 20 s. Secondly, ER was administered in a total dose of 40 μg into the RCA and of 64 μg into the LCA over 2-4 min. Intracoronary injection of ACh and ER provoked spasm in 221 patients consisting of 160 male patients and 61 female patients. In female patients, the spasm provoked by ACh was almost perfect except in two patients (59 patients, 96.7 %), while ER provoked spasm in only 20 patients (32.8 %). In male patients, provoked spasm by ACh (129 patients, 80.6 %) was significantly higher than ER (97 patients, 60.6 %). As a spasm provocation test, ACh is more sensitive than ER in both sexes and especially in females. We may select two pharmacological agents by sex differences to provoke coronary artery spasm in the cardiac catheterization laboratory in the future. PMID:25539623

  6. In vitro evaluation of matrix metalloproteinases as predictive testing for nickel, a model sensitizing agent

    International Nuclear Information System (INIS)

    The identification of potential damage due to chemical exposure in the workplace is a major health and regulatory concern. Traditional tests that measure both sensitization and elicitation responses require the use of animals. An alternative to this widespread use of experimental animals could have a crucial impact on risk assessment, especially for the preliminary screening of new molecules. We developed an in vitro model for the screening of potential toxic compounds. Human keratinocytes (HaCat) were used as target cells while matrix metalloproteinases (MMP) were selected as responders because they are key enzymes involved in extracellular matrix (ECM) degradation in physiological and pathological conditions. Chemical exposure was performed using nickel sulphate as a positive tester. Nickel contact induced upregulation of MMP-2 and IL-8 mRNA production. Molecular activation occurred even at very low nickel concentrations even though no phenotypic changes were observed. MMP-9 accumulation was found in the medium of treated cells with respect to controls. These observations led to the hypothesis that even minimal exposure can accumulate transcriptional activity resulting in long-term clinical signs after contact. Our simple in vitro model can be applied as a useful preliminary complement to the animal studies to screen the effects of new potential toxic compounds

  7. N-isopropyl-p-I-123-Iodoamphetamine is a sensitive test for detecting malignant melanoma

    International Nuclear Information System (INIS)

    N-isopropyl-p-I-123-Iodoamphetamine (I-123-IMP) was originally developed for the measurement of the brain blood flow. I-123-IMP is known to be incorporated into melanin-producing cells suggesting that I-123-IMP is incorporated in malignant melnoma. We tested both I-123-IMP and Ga-67 citrate in 36 cases with malignant melanoma in order to compare their clinical utility in the same patients. Of the 22 primary lesions, 11 (50%) were detected by I-123-IMP scan, but only 6 (22.7%) were detected by Ga-67 citrate scan. Of the 28 metastatic lesions, 15 (53.6%) were detected by I-123-IMP scan, but only 13 (46.4%) were detected by Ga-67 citrate scan. Among the I-123-IMP scans, there were no false positive cases, but Ga-67 citrate detected post operative lesions. In conclusion, I-123 IMP has advantages in the detection of malignant melanoma in terms of sensitivity and specificity. (author)

  8. Sensitivity and specificity of various serologic tests for detection of Toxoplasma gondii infection in naturally infected sows

    DEFF Research Database (Denmark)

    Dubey, J.P.; Thulliez, P.; Weigel, R.M.; Andrews, C.D.; Lind, Peter; Powell, E.C.

    1995-01-01

    The sensitivity and specificity of various serologic tests for antibodies to Toxoplasma gondii were compared in 1,000 naturally exposed sows, using isolation of viable T gondii as the definitive test. Serum samples obtained from heart blood of 1,000 sows from Iowa were examined for T gondii...... antibodies by use of the modified agglutination test (MAT), latex agglutination test (LAT), indirect hemagglutination test (IHAT), and ELISA. Toxoplasma gondii was isolated from 170 hearts of 1,000 sows by bioassays in mice and cats. The percentage of samples diagnosed as positive for each of the serologic...

  9. Distillation Time as Tool for Improved Antimalarial Activity and Differential Oil Composition of Cumin Seed Oil

    Science.gov (United States)

    A steam distillation extraction kinetics experiment was conducted to estimate essential oil yield, composition, antimalarial, and antioxidant capacity of cumin (Cuminum cyminum L.) seed (fruits). Furthermore, regression models were developed to predict essential oil yield and composition for a given...

  10. Development and Evaluation of a Rapid and Sensitive EBOV-RPA Test for Rapid Diagnosis of Ebola Virus Disease

    Science.gov (United States)

    Yang, Mingjuan; Ke, Yuehua; Wang, Xuesong; Ren, Hang; Liu, Wei; Lu, Huijun; Zhang, Wenyi; Liu, Shiwei; Chang, Guohui; Tian, Shuguang; Wang, Lihua; Huang, Liuyu; Liu, Chao; Yang, Ruifu; Chen, Zeliang

    2016-01-01

    Confirming Ebola virus disease (EVD), a deadly infectious disease, requires real-time RT-PCR, which takes up to a few hours to yield results. Therefore, a rapid diagnostic assay is imperative for EVD diagnosis. A rapid nucleic acid test based on recombinase polymerase amplification (EBOV-RPA) was developed to specifically detect the 2014 outbreak strains. The EBOV-RPA assay was evaluated by testing samples from suspected EVD patients in parallel with RT-PCR. An EBOV-RPA, which could be completed in 20 min, was successfully developed. Of 271 patients who tested positive for Ebola virus by RT-PCR, 264 (sensitivity: 97%, 95% CI: 95.5–99.3%) were positive by EBOV-RPA; 101 of 104 patients (specificity: 97%, 95% CI: 93.9–100%) who tested negative by RT-PCR were also negative by EBOV-RPA. The sensitivity values for samples with a Ct value of <34, which accounted for 95.59% of the samples, was 100%. Discordant samples positive by RT-PCR but negative by EBOV-RPA had significantly high Ct values. Results of external quality assessment samples with EBOV-RPA were 100%, consistent with those of RT-PCR. The EBOV-RPA assay showed 97% sensitivity and 97% specificity for all EVD samples tested, making it a rapid and sensitive test for EVD diagnosis. PMID:27246147

  11. Antimalarial qinghaosu/artemisinin: The therapy worthy of a Nobel Prize

    OpenAIRE

    Jerapan Krungkrai; Sudaratana Rochanakij Krungkrai

    2016-01-01

    Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Art...

  12. Poor quality vital anti-malarials in Africa - an urgent neglected public health priority.

    OpenAIRE

    Newton Paul N; Green Michael D; Mildenhall Dallas C; Plançon Aline; Nettey Henry; Nyadong Leonard; Hostetler Dana M; Swamidoss Isabel; Harris Glenn A; Powell Kristen; Timmermans Ans E; Amin Abdinasir A; Opuni Stephen K; Barbereau Serge; Faurant Claude

    2011-01-01

    Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African coun...

  13. Post-marketing surveillance of anti-malarial medicines used in Malawi

    OpenAIRE

    Chikowe, Ibrahim; Osei-Safo, Dorcas; Harrison, Jerry JEK; Konadu, Daniel Y; Addae-Mensah, Ivan

    2015-01-01

    Background The growing concern over the extent of anti-malarial medicine resistance in sub-Saharan Africa, driven largely by administration of sub-therapeutic doses derived from falsified and substandard medicines necessitates regular monitoring of the quality of these medicines to avert any potential public health disaster. This study aimed at determining the active pharmaceutical ingredient (API) content of anti-malarial medicines available in Malawi with respect to the manufacturers’ label...

  14. Self-Medication with Antibiotics and Antimalarials in the Community of Silte Zone, South Ethiopia

    OpenAIRE

    Nasir Tajure Wabe; Dargicho Ahmed; Mulugeta Tarekegn Angamo

    2012-01-01

    AIM: Self-medication with antibiotics and antimalarials occurs among the population in Ethiopian. We studied to estimate the prevalence of self-medication with antibiotics and antimalarials in Ethiopia and evaluate factors associated with self-medications. METHODS: A cross-sectional study was conducted on 405 households, selected from Silte Zone in South Ethiopia, using a random sampling technique by employing a pretested questionnaire. Data were analyzed using SPSS for windows version 16.0. ...

  15. Public Awareness and Identification of Counterfeit Drugs in Tanzania: A View on Antimalarial Drugs

    OpenAIRE

    Mhando, Linus; Jande, Mary B.; Liwa, Anthony; Mwita, Stanley; Marwa, Karol J.

    2016-01-01

    Background. The illicit trade in counterfeit antimalarial drugs is a major setback to the fight against malaria. Information on public awareness and ability to identify counterfeit drugs is scanty. Aim. Therefore, the present study aimed at assessing public awareness and the ability to identify counterfeit antimalarial drugs based on simple observations such as appearance of the drugs, packaging, labelling, and leaflets. Methodology. A cross-sectional study was conducted using interviewer adm...

  16. In vitro antimalarial activity of different extracts of Eremostachys macrophylla Montbr. & Auch.

    OpenAIRE

    Solmaz Asnaashari; Fariba Heshmati Afshar; Atefeh Ebrahimi; Sedigheh Bamdad Moghaddam; Abbas Delazar

    2015-01-01

    Introduction: The risk of drug resistance and the use of medicinal plants in malaria prevention and treatment have led to the search for new antimalarial compounds with natural origin. Methods: In the current study, six extracts with different polarity from aerial parts and rhizomes of Eremostachys macrophylla Montbr. & Auch., were screened for their antimalarial properties by cell-free beta-hematin formation assay. Results: Dichloromethane (DCM) extracts of both parts of plant showed s...

  17. Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

    Directory of Open Access Journals (Sweden)

    CUPO Palmira

    2001-01-01

    Full Text Available An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG prevented the execution of the skin sensitivity test (SST and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP, a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71% received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2 and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP, with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out

  18. Sensitivity of wetland methane emissions to model assumptions: application and model testing against site observations

    Directory of Open Access Journals (Sweden)

    L. Meng

    2011-06-01

    Full Text Available Methane emissions from natural wetlands and rice paddies constitute a large proportion of atmospheric methane, but the magnitude and year-to-year variation of these methane sources is still unpredictable. Here we describe and evaluate the integration of a methane biogeochemical model (CLM4Me; Riley et al., 2011 into the Community Land Model 4.0 (CLM4CN in order to better explain spatial and temporal variations in methane emissions. We test new functions for soil pH and redox potential that impact microbial methane production in soils. We also constrain aerenchyma in plants in always-inundated areas in order to better represent wetland vegetation. Satellite inundated fraction is explicitly prescribed in the model because there are large differences between simulated fractional inundation and satellite observations. A rice paddy module is also incorporated into the model, where the fraction of land used for rice production is explicitly prescribed. The model is evaluated at the site level with vegetation cover and water table prescribed from measurements. Explicit site level evaluations of simulated methane emissions are quite different than evaluating the grid cell averaged emissions against available measurements. Using a baseline set of parameter values, our model-estimated average global wetland emissions for the period 1993–2004 were 256 Tg CH4 yr−1, and rice paddy emissions in the year 2000 were 42 Tg CH4 yr−1. Tropical wetlands contributed 201 Tg CH4 yr−1, or 78 % of the global wetland flux. Northern latitude (>50 N systems contributed 12 Tg CH4 yr−1. We expect this latter number may be an underestimate due to the low high-latitude inundated area captured by satellites and unrealistically low high-latitude productivity and soil carbon predicted by CLM4. Sensitivity analysis showed a large range (150–346 Tg CH4 yr−1 in

  19. Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application.

    Science.gov (United States)

    Cupo, P; de Azevedo-Marques, M M; Sarti, W; Hering, S E

    2001-01-01

    An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a

  20. Fast Responding Pressure-Sensitive Paint for Large-Scale Wind Tunnel Testing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed work focuses on implementing fast-response pressure-sensitive paint for measurements of unsteady pressure in rotorcraft applications. Significant...

  1. The failure of routine rapid HIV testing: a case study of improving low sensitivity in the field

    Directory of Open Access Journals (Sweden)

    de Azevedo Virginia

    2010-03-01

    Full Text Available Abstract Background The rapid HIV antibody test is the diagnostic tool of choice in low and middle-income countries. Previous evidence suggests that rapid HIV diagnostic tests may underperform in the field, failing to detect a substantial number of infections. A research study inadvertently discovered that a clinic rapid HIV testing process was failing to detect cases of established (high antibody titer infection, exhibiting an estimated 68.7% sensitivity (95% CI [41.3%-89.0%] over the course of the first three weeks of observation. The setting is a public service clinic that provides STI diagnosis and treatment in an impoverished, peri-urban community outside of Cape Town, South Africa. Methods The researchers and local health administrators collaborated to investigate the cause of the poor test performance and make necessary corrections. The clinic changed the brand of rapid test being used and later introduced quality improvement measures. Observations were made of the clinic staff as they administered rapid HIV tests to real patients. Estimated testing sensitivity was calculated as the number of rapid HIV test positive individuals detected by the clinic divided by this number plus the number of PCR positive, highly reactive 3rd generation ELISA patients identified among those who were rapid test negative at the clinic. Results In the period of five months after the clinic made the switch of rapid HIV tests, estimated sensitivity improved to 93.5% (95% CI [86.5%-97.6%], during which time observations of counselors administering tests at the clinic found poor adherence to the recommended testing protocol. Quality improvement measures were implemented and estimated sensitivity rose to 95.1% (95% CI [83.5%-99.4%] during the final two months of full observation. Conclusions Poor testing procedure in the field can lead to exceedingly low levels of rapid HIV test sensitivity, making it imperative that stringent quality control measures are

  2. Antimalarial Drug Resistance: Surveillance and Molecular Methods for National Malaria Control Programmes

    Directory of Open Access Journals (Sweden)

    Umberto D'Alessandro

    1998-09-01

    Full Text Available National malaria control programmes have the responsibility to develop a policy for malaria disease management based on a set of defined criteria as efficacy, side effects, costs and compliance. These will fluctuate over time and national guidelines will require periodic re-assessment and revision. Changing a drug policy is a major undertaking that can take several years before being fully operational. The standard methods on which a decision can be taken are the in vivo and the in vitro tests. The latter allow a quantitative measurement of the drug response and the assessment of several drugs at once. However, in terms of drug policy change its results might be difficult to interpret although they may be used as an early warning system for 2nd or 3rd line drugs. The new WHO 14-days in vivo test addresses mainly the problem of treatment failure and of haematological parameters changes in sick children. It gives valuable information on whether a drug still `works'. None of these methods are well suited for large-scale studies. Molecular methods based on detection of mutations in parasite molecules targeted by antimalarial drugs could be attractive tools for surveillance. However, their relationship with in vivo test results needs to be established

  3. The search for new antimalarial drugs from plants used to treat fever and malaria or plants ramdomly selected: a review

    Directory of Open Access Journals (Sweden)

    Krettli Antoniana U

    2001-01-01

    Full Text Available In this review we discuss the ongoing situation of human malaria in the Brazilian Amazon, where it is endemic causing over 610,000 new acute cases yearly, a number which is on the increase. This is partly a result of drug resistant parasites and new antimalarial drugs are urgently needed. The approaches we have used in the search of new drugs during decades are now reviewed and include ethnopharmocology, plants randomly selected, extracts or isolated substances from plants shown to be active against the blood stage parasites in our previous studies. Emphasis is given on the medicinal plant Bidens pilosa, proven to be active against the parasite blood stages in tests using freshly prepared plant extracts. The anti-sporozoite activity of one plant used in the Brazilian endemic area to prevent malaria is also described, the so called "Indian beer" (Ampelozizyphus amazonicus, Rhamnaceae. Freshly prepared extracts from the roots of this plant were totally inactive against blood stage parasites, but active against sporozoites of Plasmodium gallinaceum or the primary exoerythrocytic stages reducing tissue parasitism in inoculated chickens. This result will be of practical importance if confirmed in mammalian malaria. Problems and perspectives in the search for antimalarial drugs are discussed as well as the toxicological and clinical trials to validate some of the active plants for public health use in Brazil.

  4. Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities.

    Science.gov (United States)

    Beteck, Richard M; Coertzen, Dina; Smit, Frans J; Birkholtz, Lyn-Marie; Haynes, Richard K; N'Da, David D

    2016-07-01

    As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases. The quinolone decoquinate (DQ), an old and inexpensive coccidiostat, displays anti-malarial activity in vitro against Plasmodium falciparum (Pf). However, because of its exceedingly poor solubility in water or organic solvents, development of DQ as a drug is problematical. We have therefore converted DQ in straightforward fashion into tractable new derivatives that display good activities in vitro against chloroquine-sensitive NF54 and multidrug-resistant K1 and W2 Pf, and relatively low toxicities against human fibroblast cells. The most active compound, the N-acetyl derivative 30, is 5-fold more active than DQ against NF54 and K1 and equipotent with DQ against W2. It possesses an activity profile against all strains comparable with that of the artemisinin derivative artesunate. Overall, this compound and the other accessible and active derivatives serve as an attractive template for development of new and economic lead quinolones. PMID:27210430

  5. Searching for a more sensitive earthworm species to be used in pesticide homologation tests - a meta-analysis.

    Science.gov (United States)

    Pelosi, C; Joimel, S; Makowski, D

    2013-01-01

    Pesticide risk assessments include experiments designed to measure the effect of pesticides on earthworms using the Eisenia fetida fetida or Eisenia fetida andrei species. There is no clear consensus in the literature on the sensitivity of different earthworm species to pesticides. We performed a meta-analysis on the sensitivity of several earthworm species to pesticides to determine the most sensitive species, and to discuss their suitability for European homologation tests. A dataset including median lethal dose (LC50) values reported in 44 experimental treatments was constructed and then analyzed in order to compare the sensitivity levels of E. fetida with that of other earthworm species. Results showed that LC50 values reported for Lumbricus terrestris and Aporrectodea caliginosa were on average significantly lower than for E. fetida. Considering the relatively high LC50 values reported for E. fetida and the absence of this species from zones where pesticides are usually applied, the relevance of using E. fetida for pesticide homologation tests is questionable and we advise risk assessors to use A. caliginosa as model species. A new protocol based on this species could be proposed for European homologation tests but its implementation will require the definition of a new standard and take time. In the meantime, the results obtained with E. fetida should be interpreted with caution taking into account the low sensitivity of this species. Our study illustrates the value of the meta-analysis approach for comparing the sensitivity of different earthworm species to pesticides. It would be useful to extend the dataset presented in this paper in order to analyze the sensitivity of other aquatic or terrestrial organism groups used for pesticide homologation or ecotoxicology tests. PMID:23084259

  6. Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

    DEFF Research Database (Denmark)

    Juhl, Gitte Irene; Jensen, Troels Staehelin; Nørholt, Svend Erik; Svensson, Peter

    2008-01-01

    <0.05). CONCLUSION: We found clear signs of sensitization of the trigeminal nociceptive system for at least one week after the surgery. Our results indicate that even a minor orofacial surgical procedure may be sufficient to evoke signs of both central and peripheral sensitization, which may play a...

  7. Evaluation of human skin tests for potential dermal irritant and contact sensitizing products: a position paper

    NARCIS (Netherlands)

    Loveren H van; Jong WH de; Garssen J; LPI

    1998-01-01

    Prediction of human cutaneous irritation and sensitization in view of hazard identification has primarily relied on the use of laboratory animals. Such studies in laboratory animals have been very instrumental in the detection of potential contact sensitizing agents. There are however many uncertain

  8. Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

    Directory of Open Access Journals (Sweden)

    Rusk Andria

    2012-08-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could

  9. An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

    Science.gov (United States)

    Najer, Adrian; Wu, Dalin; Nussbaumer, Martin G.; Schwertz, Geoffrey; Schwab, Anatol; Witschel, Matthias C.; Schäfer, Anja; Diederich, François; Rottmann, Matthias; Palivan, Cornelia G.; Beck, Hans-Peter; Meier, Wolfgang

    2016-08-01

    Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol-disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30-50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL-1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (+/-)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block.Medical applications of anticancer and antimalarial drugs often suffer from low aqueous

  10. Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications

    Directory of Open Access Journals (Sweden)

    Chance Michael L

    2011-08-01

    Full Text Available Abstract Background This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP. Methods Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr-C59R and dihydropteroate synthase (dhps-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Results Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9. The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. Conclusion This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum

  11. Exploring QSAR for Antimalarial Activities and Drug Distribution within Blood of a Series of 4-Aminoquinoline Drugs Using Genetic-MLR

    Directory of Open Access Journals (Sweden)

    Amir Najafi

    2013-01-01

    Full Text Available Malaria has been one of the most significant public health problems for centuries. QSAR modeling of the antimalarial activity and blood-to-plasma concentration ratio of Chloroquine and a new series of 4-aminoquinoline derivatives were developed using genetic algorithms with multiple linear regression (GA-MLR method. We obtained two different models against Chloroquine-sensitive (3D7 and Chloroquine-resistant (W2 strains of Plasmodium falciparum with good adjustment levels. Drug distribution in blood, defined as drug blood-to-plasma concentration ratio (Rb, is related to molecular descriptors. Leave-many-out (LMO and Y-randomization methods confirmed the models' robustness.

  12. Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery

    OpenAIRE

    Sara E. McCarty; Amanda Schellenberger; Douglas C. Goodwin; Ngolui Rene Fuanta; Tekwani, Babu L.; Calderón, Angela I.

    2015-01-01

    The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed to maintain redox equilibrium in Plasmodium species, is a promising target for new antimalarials. This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences...

  13. Sensitivity analysis, calibration, and testing of a distributed hydrological model using error-based weighting and one objective function

    Science.gov (United States)

    Foglia, L.; Hill, M.C.; Mehl, S.W.; Burlando, P.

    2009-01-01

    We evaluate the utility of three interrelated means of using data to calibrate the fully distributed rainfall-runoff model TOPKAPI as applied to the Maggia Valley drainage area in Switzerland. The use of error-based weighting of observation and prior information data, local sensitivity analysis, and single-objective function nonlinear regression provides quantitative evaluation of sensitivity of the 35 model parameters to the data, identification of data types most important to the calibration, and identification of correlations among parameters that contribute to nonuniqueness. Sensitivity analysis required only 71 model runs, and regression required about 50 model runs. The approach presented appears to be ideal for evaluation of models with long run times or as a preliminary step to more computationally demanding methods. The statistics used include composite scaled sensitivities, parameter correlation coefficients, leverage, Cook's D, and DFBETAS. Tests suggest predictive ability of the calibrated model typical of hydrologic models. Copyright 2009 by the American Geophysical Union.

  14. A Monte Carlo Examination of the Sensitivity of the Differential Functioning of Items and Tests Framework for Tests of Measurement Invariance with Likert Data

    Science.gov (United States)

    Meade, Adam W.; Lautenschlager, Gary J.; Johnson, Emily C.

    2007-01-01

    This article highlights issues associated with the use of the differential functioning of items and tests (DFIT) methodology for assessing measurement invariance (or differential functioning) with Likert-type data. Monte Carlo analyses indicate relatively low sensitivity of the DFIT methodology for identifying differential item functioning (DIF)…

  15. Assessment of Antimalarial Activity against Plasmodium falciparum and Phytochemical Screening of Some Yemeni Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Mohammed A. Alshawsh

    2009-01-01

    Full Text Available Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa, Azadirachta indica, Cissus rotundifolia, Echium rauwalfii, Dendrosicyos socotrana and Boswellia elongata commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates of Plasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured by in vitro micro test (Mark III according to World Health Organization (WHO 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50 values less than 4 µg/ml, namely the water extracts of A. fruticosa, A. indica and D. socotrana. Six extracts showed moderate activity with IC50 values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50 values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides.

  16. An integrated electrochemical device based on immunochromatographic test strip and enzyme labels for sensitive detection of disease-related biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Zhexiang; Wang, Jun; Wang, Hua; Li, Yao Q.; Lin, Yuehe

    2012-05-30

    A novel electrochemical biosensing device that integrates an immunochromatographic test strip and a screen-printed electrode (SPE) connected to a portable electrochemical analyzer was presented for rapid, sensitive, and quantitative detection of disease-related biomarker in human blood samples. The principle of the sensor is based on sandwich immunoreactions between a biomarker and a pair of its antibodies on the test strip, followed by highly sensitive square-wave voltammetry (SWV) detection. Horseradish peroxidase (HRP) was used as a signal reporter for electrochemical readout. Hepatitis B surface antigen (HBsAg) was employed as a model protein biomarker to demonstrate the analytical performance of the sensor in this study. Some critical parameters governing the performance of the sensor were investigated in detail. The sensor was further utilized to detect HBsAg in human plasma with an average recovery of 91.3%. In comparison, a colorimetric immunochromatographic test strip assay (ITSA) was also conducted. The result shows that the SWV detection in the electrochemical sensor is much more sensitive for the quantitative determination of HBsAg than the colorimetric detection, indicating that such a sensor is a promising platform for rapid and sensitive point-of-care testing/screening of disease-related biomarkers in a large population

  17. A simple and sensitive quality control method of the anaerobic atmosphere for identification and antimicrobial susceptibility testing of anaerobic bacteria

    DEFF Research Database (Denmark)

    Justesen, Tage; Justesen, Ulrik Stenz

    2013-01-01

    The maintenance of a strict anaerobic atmosphere is essential for the culture of strict anaerobic bacteria. We describe a simple and sensitive quality control method of the anaerobic atmosphere, based on the measurement of the zone diameter around a 5-μg metronidazole disk when testing an...

  18. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian;

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...... (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity...... (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were...

  19. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists.

    Science.gov (United States)

    Ross, Rebecca E; Nimmo-Smith, W Alex M; Howell, Kerry L

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models' abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation. PMID:27575625

  20. Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists

    Science.gov (United States)

    Nimmo-Smith, W. Alex M.; Howell, Kerry L.

    2016-01-01

    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models’ abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation. PMID

  1. Comparative sensitivities of exercise, isoproterenol infusion and cold pressor tests for detecting myocardial ischemia

    International Nuclear Information System (INIS)

    The comparative sensitivities of exercise (supine ergometer), isoproterenol (ISP) infusion and cold pressor test (CPT) for detecting myocardial ischemia in patients with effort angina (45 cases) and vasospastic angina (16 cases) were investigated. Left ventricular function was evaluated by computerized quantitative analysis using, 1) radionuclide angiography during exercise (EX-RI) and ISP infusion (ISP-RI), 2) two-dimensional echocardiography during ISP infusion (ISP-2DE) and CPT (CP-2DE) and 3) digital subtraction angiography during CPT (CP-DSA). The incidence of regional wall motion abnormalities (WMA) in patients with effort angina were as follows: 83 % in EX-RI, 80 % in ISP-2DE, 80 % in ISP-RI, 75 % in CP-2DE and 86 % in CP-DSA. In patients with vasospatic angina, the WMA were as follows: 40 % in EX-RI, 0 % in ISP-RI and 71 % in CP-DSA. In patients with atypical chest pain, the WMA were 0 % in EX-RI, 0 % in ISP-RI, 8 % in ISP-2DE, 13 % in CP-2DE and 13 % in CP-DSA. The left ventricular ejection fraction (EF) was unchanged during ISP (from 65 ± 11 % to 68 ± 12 %) and it decreased both during exercise (from 64 ± 10 % to 58 ± 9 %, p < 0.05) and during CPT (from 69 ± 10 % to 65 ± 9 %, p < 0.05) in patients with effort angina. In patients with vasospastic angina, the EF was unchanged both during exercise (from 70 ± 7 % to 68 ± 13 %) and during the CPT (from 76 ± 5 % to 75 ± 4 %), while it increased during ISP infusion (from 63 ± 8 % to 79 ± 7 %, p < 0.01). In patients with atypical chest pain, the EF was increased both during exercise (from 72 ± 7 % to 79 ± 5 %, p < 0.01) and during ISP infusion (from 67 ± 5 % to 78 ± 7 %, p < 0.01), while it was unchanged during CPT (from 77 ± 7 % to 76 ± 8 %). (J.P.N.)

  2. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

    Science.gov (United States)

    Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N.; Khan, Wasif Ali

    2016-01-01

    Background The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Methods Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Results Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. Conclusion The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal

  3. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Benedikt Ley

    Full Text Available The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2 plus single dose primaquine (0.75mg/kg on day2 for P. falciparum infections, or with chloroquine (days 0-2 plus 14 days primaquine (3.5mg/kg total over 14 days for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374.Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections. Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3 hours for P. falciparum, 20.0 (IQR: 9.5-22.7 hours for P. vivax and 16.6 (IQR: 10.0-46.0 hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174 had severe G6PD deficiency (<10% activity, five participants (5/174 had mild G6PD deficiency (10-60% activity. The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0% and -7.4% (95%CI: -4.5 to -10.4% respectively.The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather

  4. Cytotoxicity of antimalarial plant extracts from Kenyan biodiversity to the brine shrimp, Artemia salina L. (Artemiidae

    Directory of Open Access Journals (Sweden)

    Joseph Mwanzia Nguta

    2012-07-01

    Full Text Available Artemia salina (Artemiidae, the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemicals and natural products. In this study the medium lethal concentration fifty (LC50 values of 45 antimalarial plant extracts and positive controls, cyclophosphamide and etoposide were determined using Artemia salina (Artemiidae. Out of the 45 organic extracts screened for activity against Artemia salina larvae, 23 (51% of the crude extracts demonstrated activity at or below 100 μg/mL, and were categorized as having strong cytotoxic activity, 18 (40% of the crude extracts had LC50 values between 100 μg/mL and 500 μg/mL, and were categorized as having moderate cytotoxicity, 2 (4.5% of the crude extracts had LC50 values between 500 μg/mL and 1000 μg/mL, and were considered to have weak cytotoxic activity, while 2 (4.5% of the crude extracts had LC50 values greater than 1000 μg/mL and were considered to be non toxic. Approximately 20% (9 of the aqueous extracts demonstrated activity at or below 100 g/mL and were considered to have strong cytotoxic activity, 40% (18 of the screened aqueous crude extracts had LC50 values between 100 μg/mL and 500 μg/mL and were considered to be moderately cytotoxic, 16% (7 of the crude extracts had LC50 values between 500 μg/mL and 1000 μg/mL and were considered to have weak cytotoxic activity while 24% (11 of the aqueous extracts had LC50 values greater than 1000μg/mL and were categorized as non toxic The positive controls, cyclophosphamide and etoposide exhibited strong cytotoxicity with LC50 values of 95 μg/mL and 6 μg/mL respectively in a 24 hour lethality study, validating their use as anticancer agents. In the current study, 95.5% of all the screened organic extracts and 76% of the investigated aqueous extracts demonstrated LC50 values <1000 g/mL, indicating that these plants could not make safe anti-malarial treatments. This calls for dose adjustment amongst the

  5. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

    Science.gov (United States)

    Shen, Shuo; Liu, Shu-Zhi; Zhang, Yu-Shi; Du, Mao-Bo; Liang, Ai-Hua; Song, Li-Hua; Ye, Zu-Guang

    2015-01-01

    Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic. PMID:26170661

  6. Sensitivity analysis on the interfacial drag in SPACE code to simulate UPTF separate effect test about loop seal clearance phenomenon

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sukho; Lim, Sanggyu; You, Gukjong; Park, Youngsheop [Korea Hydro and Nuclear Power Company, Ltd., Daejeon (Korea, Republic of)

    2014-05-15

    The nuclear thermal hydraulic system code known as SPACE (Safety and Performance Analysis CodE) was developed and its V and V (Verification and Validation) have been conducted using well-known SETs (Separate Effect Tests) and IETs (Integral Effect Tests). At the same time, the SBLOCA (Small Break Loss of Coolant Accident) methodology in accordance with Appendix K of 10CFR50 for the APR1400 (Advanced Power Reactor 1400) was developed and applied to regulatory body for licensing in 2013. Especially, the SBLOCA methodology developed using SPACE v2.14 code adopts inherent test matrix independent of V and V test to show its conservatism for important phenomena. In this paper, the predictability of SPACE code for UPTF (Upper Plenum Test Facility) test simulating loop seal clearance of SBLOCA important phenomena and the related sensitivity analysis are introduced.

  7. Sensitivity analysis on the interfacial drag in SPACE code to simulate UPTF separate effect test about loop seal clearance phenomenon

    International Nuclear Information System (INIS)

    The nuclear thermal hydraulic system code known as SPACE (Safety and Performance Analysis CodE) was developed and its V and V (Verification and Validation) have been conducted using well-known SETs (Separate Effect Tests) and IETs (Integral Effect Tests). At the same time, the SBLOCA (Small Break Loss of Coolant Accident) methodology in accordance with Appendix K of 10CFR50 for the APR1400 (Advanced Power Reactor 1400) was developed and applied to regulatory body for licensing in 2013. Especially, the SBLOCA methodology developed using SPACE v2.14 code adopts inherent test matrix independent of V and V test to show its conservatism for important phenomena. In this paper, the predictability of SPACE code for UPTF (Upper Plenum Test Facility) test simulating loop seal clearance of SBLOCA important phenomena and the related sensitivity analysis are introduced

  8. Tests of a novel method to assay SNM using polarized photofission and its sensitivity in the presence of shielding

    International Nuclear Information System (INIS)

    A novel method to identify Special Nuclear Material was recently developed (Mueller et al., 2014) [1]. This method relies upon using a linearly polarized γ-ray beam to induce photofission of a sample and then comparing the prompt fission neutron yields in and out of the plane of beam polarization. The present paper will describe experimental tests of this new technique and assess its sensitivity in the presence of shielding. The capability of this technique to measure the enrichment of uranium was tested by using combinations of thin 235U and 238U foils of known enrichments. The sensitivity of this assay to shielding by lead, steel, and polyethylene was experimentally measured and simulated using GEANT4. These tests show that the measured asymmetry can indeed be used to determine the enrichment of materials composed of an admixture of 235U and 238U, and this asymmetry is relatively insensitive to moderate amounts of shielding

  9. Contrast sensitivity test and conventional and high frequency audiometry: information beyond that required to prescribe lenses and headsets

    Science.gov (United States)

    Comastri, S. A.; Martin, G.; Simon, J. M.; Angarano, C.; Dominguez, S.; Luzzi, F.; Lanusse, M.; Ranieri, M. V.; Boccio, C. M.

    2008-04-01

    In Optometry and in Audiology, the routine tests to prescribe correction lenses and headsets are respectively the visual acuity test (the first chart with letters was developed by Snellen in 1862) and conventional pure tone audiometry (the first audiometer with electrical current was devised by Hartmann in 1878). At present there are psychophysical non invasive tests that, besides evaluating visual and auditory performance globally and even in cases catalogued as normal according to routine tests, supply early information regarding diseases such as diabetes, hypertension, renal failure, cardiovascular problems, etc. Concerning Optometry, one of these tests is the achromatic luminance contrast sensitivity test (introduced by Schade in 1956). Concerning Audiology, one of these tests is high frequency pure tone audiometry (introduced a few decades ago) which yields information relative to pathologies affecting the basal cochlea and complements data resulting from conventional audiometry. These utilities of the contrast sensitivity test and of pure tone audiometry derive from the facts that Fourier components constitute the basis to synthesize stimuli present at the entrance of the visual and auditory systems; that these systems responses depend on frequencies and that the patient's psychophysical state affects frequency processing. The frequency of interest in the former test is the effective spatial frequency (inverse of the angle subtended at the eye by a cycle of a sinusoidal grating and measured in cycles/degree) and, in the latter, the temporal frequency (measured in cycles/sec). Both tests have similar duration and consist in determining the patient's threshold (corresponding to the inverse multiplicative of the contrast or to the inverse additive of the sound intensity level) for each harmonic stimulus present at the system entrance (sinusoidal grating or pure tone sound). In this article the frequencies, standard normality curves and abnormal threshold shifts

  10. Antimalarial activity of ruthenium(II) and osmium(II) arene complexes with mono- and bidentate chloroquine analogue ligands.

    Science.gov (United States)

    Ekengard, Erik; Glans, Lotta; Cassells, Irwin; Fogeron, Thibault; Govender, Preshendren; Stringer, Tameryn; Chellan, Prinessa; Lisensky, George C; Hersh, William H; Doverbratt, Isa; Lidin, Sven; de Kock, Carmen; Smith, Peter J; Smith, Gregory S; Nordlander, Ebbe

    2015-11-28

    Eight new ruthenium and five new osmium p-cymene half-sandwich complexes have been synthesized, characterized and evaluated for antimalarial activity. All complexes contain ligands that are based on a 4-chloroquinoline framework related to the antimalarial drug chloroquine. Ligands HL(1-8) are salicylaldimine derivatives, where HL(1) = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine, and HL(2-8) contain non-hydrogen substituents in the 3-position of the salicylaldimine ring, viz. F, Cl, Br, I, NO2, OMe and (t)Bu for HL(2-8), respectively. Ligand HL(9) is also a salicylaldimine-containing ligand with substitutions in both 3- and 5-positions of the salicylaldimine moiety, i.e. N-(2-((2-hydroxy-3,5-di-tert-butylphenyl)methyl-imino)ethyl)-7-chloroquinolin-4-amine, while HL(10) is N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) The half sandwich metal complexes that have been investigated are [Ru(η(6)-cym)(L(1-8))Cl] (Ru-1-Ru-8, cym = p-cymene), [Os(η(6)-cym)(L(1-3,5,7))Cl] (Os-1-Os-3, Os-5, and Os-7), [M(η(6)-cym)(HL(9))Cl2] (M = Ru, Ru-HL(9); M = Os, Os-HL(9)) and [M(η(6)-cym)(L(10))Cl]Cl (M = Ru, Ru-10; M = Os, Os-10). In complexes Ru-1-Ru-8 and Ru-10, Os-1-Os-3, Os-5 and Os-7 and Os-10, the ligands were found to coordinate as bidentate N,O- and N,N-chelates, while in complexes Ru-HL(9) and Os-HL(9), monodentate coordination of the ligands through the quinoline nitrogen was established. The antimalarial activity of the new ligands and complexes was evaluated against chloroquine sensitive (NF54 and D10) and chloroquine resistant (Dd2) Plasmodium falciparum malaria parasite strains. Coordination of ruthenium and osmium arene moieties to the ligands resulted in lower antiplasmodial activities relative to the free ligands, but the resistance index is better for the ruthenium complexes compared to chloroquine. Overall, osmium complexes appeared to be less active than the corresponding ruthenium complexes. PMID:26491831

  11. The relationship of speech intelligibility with hearing sensitivity, cognition, and perceived hearing difficulties varies for different speech perception tests

    Directory of Open Access Journals (Sweden)

    Antje eHeinrich

    2015-06-01

    Full Text Available Listeners vary in their ability to understand speech in noisy environments. Hearing sensitivity, as measured by pure-tone audiometry, can only partly explain these results, and cognition has emerged as another key concept. Although cognition relates to speech perception, the exact nature of the relationship remains to be fully understood. This study investigates how different aspects of cognition, particularly working memory and attention, relate to speech intelligibility for various tests.Perceptual accuracy of speech perception represents just one aspect of functioning in a listening environment. Activity and participation limits imposed by hearing loss, in addition to the demands of a listening environment, are also important and may be better captured by self-report questionnaires. Understanding how speech perception relates to self-reported aspects of listening forms the second focus of the study.Forty-four listeners aged between 50-74 years with mild SNHL were tested on speech perception tests differing in complexity from low (phoneme discrimination in quiet, to medium (digit triplet perception in speech-shaped noise to high (sentence perception in modulated noise; cognitive tests of attention, memory, and nonverbal IQ; and self-report questionnaires of general health-related and hearing-specific quality of life.Hearing sensitivity and cognition related to intelligibility differently depending on the speech test: neither was important for phoneme discrimination, hearing sensitivity alone was important for digit triplet perception, and hearing and cognition together played a role in sentence perception. Self-reported aspects of auditory functioning were correlated with speech intelligibility to different degrees, with digit triplets in noise showing the richest pattern. The results suggest that intelligibility tests can vary in their auditory and cognitive demands and their sensitivity to the challenges that auditory environments pose on

  12. The relationship of speech intelligibility with hearing sensitivity, cognition, and perceived hearing difficulties varies for different speech perception tests.

    Science.gov (United States)

    Heinrich, Antje; Henshaw, Helen; Ferguson, Melanie A

    2015-01-01

    Listeners vary in their ability to understand speech in noisy environments. Hearing sensitivity, as measured by pure-tone audiometry, can only partly explain these results, and cognition has emerged as another key concept. Although cognition relates to speech perception, the exact nature of the relationship remains to be fully understood. This study investigates how different aspects of cognition, particularly working memory and attention, relate to speech intelligibility for various tests. Perceptual accuracy of speech perception represents just one aspect of functioning in a listening environment. Activity and participation limits imposed by hearing loss, in addition to the demands of a listening environment, are also important and may be better captured by self-report questionnaires. Understanding how speech perception relates to self-reported aspects of listening forms the second focus of the study. Forty-four listeners aged between 50 and 74 years with mild sensorineural hearing loss were tested on speech perception tests differing in complexity from low (phoneme discrimination in quiet), to medium (digit triplet perception in speech-shaped noise) to high (sentence perception in modulated noise); cognitive tests of attention, memory, and non-verbal intelligence quotient; and self-report questionnaires of general health-related and hearing-specific quality of life. Hearing sensitivity and cognition related to intelligibility differently depending on the speech test: neither was important for phoneme discrimination, hearing sensitivity alone was important for digit triplet perception, and hearing and cognition together played a role in sentence perception. Self-reported aspects of auditory functioning were correlated with speech intelligibility to different degrees, with digit triplets in noise showing the richest pattern. The results suggest that intelligibility tests can vary in their auditory and cognitive demands and their sensitivity to the challenges that

  13. Insights following change in drug policy: A descriptive study for antimalarial prescription practices in children of public sector health facilities in Jharkhand state of India

    Directory of Open Access Journals (Sweden)

    Neelima Mishra

    2013-12-01

    Full Text Available Background & objectives: Widespread resistance to chloroquine was the mainstay to implement artemisininbased combination therapy (ACT in the year 2007 in few malaria endemic states in India including Jharkhand as the first line of treatment for uncomplicated Plasmodium falciparum malaria. This study was conducted in Jharkhand state of the country just after the implementation of ACT to assess the prevailing antimalarial drug prescribing practices, availability of antimalarial drugs and the acceptability of the new policy by the health professionals for the treatment of uncomplicated P. falciparum malaria patients particularly in children ≤15 yr of age. Methods: This is a cross-sectional study in children aged ≤15 yr with malaria or to whom antimalarial drug was prescribed. Main outcome measure was prescription of recommended ACT in children aged ≤15 yr with malaria in the selected areas of Jharkhand. Results: In the year 2008, artemisinin-based combination therapy (ACT was implemented in 12 districts of the studied state; however, the availability of ACT was confirmed only in five districts. Antimalarial prescription was prevalent amongst the undiagnosed (8.4%, malaria negative (64.3% and unknown blood test result (1.2% suggesting the prevalence of irrational treatment practices. ACT prescription was very low with only 3.2% of confirmed falciparum malaria patients receiving it while others received either non-artesunate (NA treatment (88.1% including chloroquine (CQ alone, CQ + Primaquine (PQ/other drugs, sulphadoxine-pyrimethamine (SP alone, SP + other drugs or artemisinin monotherapy (AM treatment (6.3%. Still others were given nonantimalarial treatment (NM in both malaria positive (0.3% and malaria negative (2.1% cases. Interpretation & conclusion: Despite the change in drug policy in the studied state the availability and implementation of ACT was a major concern. Nevertheless, the non-availability of blister packs for children aged

  14. Targeting Plasmodium Metabolism to Improve Antimalarial Drug Design.

    Science.gov (United States)

    Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Betancourt-Conde, Irene; Aguirre-Raudry, Miriam; Vázquez-Raygoza, Alejandra; Luevano-De la Cruz, Artemisa; Favela-Candia, Alejandro; Sarabia-Sanchez, Marie; Ríos-Soto, Lluvia; Méndez-Hernández, Edna; Cisneros-Martínez, Jorge; Palacio-Gastélum, Marcelo Gómez; Valdez-Solana, Mónica; Hernández-Rivera, Jessica; De Lira-Sánchez, Jaime; Campos-Almazán, Mara; Téllez-Valencia, Alfredo

    2016-01-01

    Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria. PMID:26983887

  15. Tests of a position sensitive photomultiplier and measurement of diffraction pattern by counting single photons

    International Nuclear Information System (INIS)

    The present paper describes a laboratory course held at the ICFA'99 Instrumentation School in Istanbul, Turkey. This course intends to introduce position sensitive multianode photomultiplier tubes (Hamamatsu R5900 type M16 and L16). Using a light emitting diode, the student will measure position sensitivity by scanning the light spot across the M16 PMT. The second part of the exercise consists of measuring a diffraction pattern produced by light passing through a slit. For this purpose the L16 PMT is used and the students attention is drawn to the pedagogical problem of wave-particle duality

  16. Central sensitization phenomena after third molar surgery: A quantitative sensory testing study

    DEFF Research Database (Denmark)

    Jensen, T.S.; Norholt, S.E.; Svensson, P.;

    2008-01-01

    Background: Surgical removal of third molars may carry a risk of developing persistent orofacial pain, and central sensitization appears to play an important role in the transition from acute to chronic pain. Aim: The aim of this study was to investigate sensitization (primarily central sensitiza......, which may play a role in the transition from acute to chronic pain in susceptible individuals. (c) 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/1...

  17. Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities.

    Science.gov (United States)

    Karad, Sharad C; Purohit, Vishal B; Thakor, Parth; Thakkar, Vasudev R; Raval, Dipak K

    2016-04-13

    A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level. PMID:26900659

  18. Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery

    Science.gov (United States)

    Pradhan, Anupam; Siwo, Geoffrey H.; Singh, Naresh; Martens, Brian; Balu, Bharath; Button-Simons, Katrina A.; Tan, Asako; Zhang, Min; Udenze, Kenneth O.; Jiang, Rays H.Y.; Ferdig, Michael T.; Adams, John H.; Kyle, Dennis E.

    2015-01-01

    The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs’ mechanisms of action. A mutant of the artemisinin resistance candidate gene - “K13-propeller” gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways. PMID:26541648

  19. Novel Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Booker, Michael L.; Bastos, Cecilia M.; Kramer, Martin L.; Barker, Jr., Robert H.; Skerlj, Renato; Sidhu, Amar Bir; Deng, Xiaoyi; Celatka, Cassandra; Cortese, Joseph F.; Guerrero Bravo, Jose E.; Crespo Llado, Keila N.; Serrano, Adelfa E.; Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Viera, Sara; Garuti, Helen; Wittlin, Sergio; Papastogiannidis, Petros; Lin, Jing-wen; Janse, Chris J.; Khan, Shahid M.; Duraisingh, Manoj; Coleman, Bradley; Goldsmith, Elizabeth J.; Phillips, Margaret A.; Munoz, Benito; Wirth, Dyann F.; Klinger, Jeffrey D.; Wiegand, Roger; Sybertz, Edmund (Leiden-MC); (Puerto Rico); (STPHI); (Harvard); (GSK); (Genzyme); (UTSMC)

    2010-11-22

    Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high throughput screen and subsequent medicinal chemistry program identified a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH from P. falciparum, P. vivax, and P. berghei. The compounds were selective for the parasite enzymes over human DHODH, and x-ray structural data on the analog Genz-667348, demonstrated that species selectivity could be attributed to amino acid differences in the inhibitor-binding site. Compounds from this series demonstrated in vitro potency against the 3D7 and Dd2 strains of P. falciparum, good tolerability and oral exposure in the mouse, and ED{sub 50} values in the 4-day murine P. berghei efficacy model of 13-21 mg/kg/day with oral twice-daily dosing. In particular, treatment with Genz-667348 at 100 mg/kg/day resulted in sterile cure. Two recent analogs of Genz-667348 are currently undergoing pilot toxicity testing to determine suitability as clinical development candidates.

  20. 77 FR 52333 - International Workshop on Alternatives to the Murine Histamine Sensitization Test (HIST) for...

    Science.gov (United States)

    2012-08-29

    ... of animals in vaccine safety testing. The goal is to address the path toward global validation... challenges requiring frequent retesting, thereby increasing vaccine testing expense and animal usage. An..., and Replace the Use of Animals in Vaccine Potency and Safety Testing: State of the Science and...

  1. p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

    OpenAIRE

    Thyssen, JP; Andersen, KE; Bruze, M; Diepgen, T.; Giménez-Arnau, AM; Gonçalo, Margarida; Goossens, A; Le Coz, C; McFadden, J.; Rustemeyer, T.; White, IR; White, JM; Johansen, JD

    2009-01-01

    BACKGROUND: Positive patch test reactions to p-phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary 'tattoos'. Cross-sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe reactions upon hair dyeing, there is a need for 'current' prevalence data on PPD sensitization. OBJECTIVES: To compare PPD patch test results from dermatitis patients tested between 2003 and 2007 in ...

  2. Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity

    NARCIS (Netherlands)

    E.C. Matsui; G.B. Diette; E.J.M. Krop; R.C. Aalberse; A.L. Smith; P.A. Eggleston

    2006-01-01

    Background High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. Objective To determine if high levels of mouse-specific IgG and IgG4 are associated with a d

  3. Materials Testing in Long Cane Design: Sensitivity, Flexibility, and Transmission of Vibration

    Science.gov (United States)

    Rodgers, Mark D.; Emerson, Robert Wall

    2005-01-01

    Different materials that are used in manufacturing long cane shafts were assessed for their ability to transmit vibration and their sensitivity to tactile information, flexibility, and durability. It was found that the less flexible a cane shaft is, the better it transmits vibrations that are useful for discriminating surface textures and that…

  4. Public Awareness and Identification of Counterfeit Drugs in Tanzania: A View on Antimalarial Drugs

    Directory of Open Access Journals (Sweden)

    Linus Mhando

    2016-01-01

    Full Text Available Background. The illicit trade in counterfeit antimalarial drugs is a major setback to the fight against malaria. Information on public awareness and ability to identify counterfeit drugs is scanty. Aim. Therefore, the present study aimed at assessing public awareness and the ability to identify counterfeit antimalarial drugs based on simple observations such as appearance of the drugs, packaging, labelling, and leaflets. Methodology. A cross-sectional study was conducted using interviewer administered structured questionnaire and a checklist. Respondents were required to spot the difference between genuine and counterfeit antimalarial drugs given to them. Data was analysed using SPSS version 20. Results. The majority of respondents, 163 (55.6%, were able to distinguish between genuine and counterfeit antimalarial drugs. Respondents with knowledge on health effects of counterfeit drugs were more likely to identify genuine and counterfeit drugs than their counterparts (P=0.003; OR = 2.95; 95% CI: 1.47–5.65. The majority of respondents, 190 (64.8%, perceived the presence of counterfeit drugs to be a big problem to the community. Conclusions. A substantial proportion of respondents were able to distinguish between genuine and counterfeit antimalarial drugs. Public empowerment in identifying counterfeit drugs by simple observations is a major step towards discouraging the market of counterfeit drugs.

  5. Targeting protein kinases in the malaria parasite: update of an antimalarial drug target.

    Science.gov (United States)

    Zhang, Veronica M; Chavchich, Marina; Waters, Norman C

    2012-01-01

    Millions of deaths each year are attributed to malaria worldwide. Transmitted through the bite of an Anopheles mosquito, infection and subsequent death from the Plasmodium species, most notably P. falciparum, can readily spread through a susceptible population. A malaria vaccine does not exist and resistance to virtually every antimalarial drug predicts that mortality and morbidity associated with this disease will increase. With only a few antimalarial drugs currently in the pipeline, new therapeutic options and novel chemotypes are desperately needed. Hit-to-Lead diversity may successfully provide novel inhibitory scaffolds when essential enzymes are targeted, for example, the plasmodial protein kinases. Throughout the entire life cycle of the malaria parasite, protein kinases are essential for growth and development. Ongoing efforts continue to characterize these kinases, while simultaneously pursuing them as antimalarial drug targets. A collection of structural data, inhibitory profiles and target validation has set the foundation and support for targeting the malarial kinome. Pursuing protein kinases as cancer drug targets has generated a wealth of information on the inhibitory strategies that can be useful for antimalarial drug discovery. In this review, progress on selected protein kinases is described. As the search for novel antimalarials continues, an understanding of the phosphor-regulatory pathways will not only validate protein kinase targets, but also will identify novel chemotypes to thwart malaria drug resistance. PMID:22242850

  6. Standard test method for electrochemical reactivation (EPR) for detecting sensitization of AISI type 304 and 304L stainless steels

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    1994-01-01

    1.1 This test method covers a laboratory procedure for conducting an electrochemical reactivation (EPR) test on AISI Type 304 and 304L (UNS No. S30400 and S30403, respectively) stainless steels. This test method can provide a nondestructive means of quantifying the degree of sensitization in these steels (1, 2, 3). This test method has found wide acceptance in studies of the effects of sensitization on intergranular corrosion and intergranular stress corrosion cracking behavior (see Terminology G15). The EPR technique has been successfully used to evaluate other stainless steels and nickel base alloys (4), but the test conditions and evaluation criteria used were modified in each case from those cited in this test method. 1.2 The values stated in SI units are to be regarded as the standard. The inch-pound units given in parentheses are for information only. 1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this...

  7. Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

    International Nuclear Information System (INIS)

    Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction

  8. Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Borelli, Flavio Antonio de Oliveira, E-mail: fborelli@cardiol.br; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R. [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil)

    2013-11-15

    Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m{sup 2}. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction.

  9. Analysis of Culture and Drug Sensitivity Tests of Mycoplasmas for 387 Patients with Nongonococcal Urethritis (Cervicitis) in Chongqing

    Institute of Scientific and Technical Information of China (English)

    翟志芳; 郝飞; 钟白玉; 黄秀英; 唐书谦; 刁庆春

    2004-01-01

    Objective: To investigate the prevalence of mycoplasma infections and the sensitivity to antibiotics among patients with nongonococcal urethritis or cervicitis (NGU) in Chongqing. Methods: 387 NGU cases with mycoplasma-positive results upon culture were analysed retrospectively. RESULTS: The majority of patients with mycoplasma infections were in the 20-40 year old age group. No significant difference was found between males and females. Ureaplasma urealyticum is the main pathogen of these NGU cases and no clear relationship between its concentration and pathogenic ability was noted. Drug sensitivity was tested against nine antibiotics; the sensitivity rates to josamycin, minocycline and doxycycline were 94.06%, 88.89% and 86.82% respectively, while the resistance rates to lincomycin, ofloxacin, azithromycin and roxthromycin were 74.94%, 42.12%, 41.60% and 40.31% in turn. Conclusions: Josamycin, minocycline and doxycycline could be used as the first choice to treat NGU with mycoplasma infections in Chongqing. It is important to select antibiotics for NGU treatment with mycoplasma infections based on the results of drug sensitivity tests.

  10. Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer?

    Science.gov (United States)

    Milicić, Valerija; Matić, Tereza Solocki; Martinek, Vjenceslav; Tomasković, Igor; Ramljak, Vesna

    2015-09-01

    Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer

  11. Multiple IgE-mediated sensitizations to enzymes after occupational exposure: evaluation by skin prick test, RAST, and immunoblot.

    Science.gov (United States)

    Zentner, A; Jeep, S; Wahl, R; Kunkel, G; Kleine-Tebbe, J

    1997-09-01

    We investigated 10 sensitized and 10 nonsensitized workers from a pharmaceutic factory who had been exposed to powdered trypsin, chymotrypsin, bromelain, papain, amylase, and lipase. Ten nonallergic subjects served as a control group. Titrated skin prick tests (SPT), RAST, and immunoblot studies were performed with all six enzymes. SPT reactivity revealed multiple sensitizations to proteolytic enzymes, i.e., papain (specifically sensitized/total number of sensitizations: 9/10), trypsin (8/10), chymotrypsin (8/10), and bromelain (7/10) and appeared to be more frequent and more pronounced than sensitizations to amylase (3/10) or lipase (3/10). The low molecular weight of proteolytic enzymes (20-30 kDa) and their biologic activity might facilitate mucosal penetration more easily and thus-compared to amylase and lipase-permit an immune response and induction of allergic hypersensitivity. Immunoblot studies demonstrated IgG-binding bands in both SPT-positive and -negative workers, indicating exposure to the enzymes, but not in 10 unexposed control subjects. IgE-binding bands of the enzymes were detected only in workers with a positive SPT reaction and/or a positive RAST result. IgG bands were more frequent and the IgG/IgE ratio was increased in workers without allergic complaints compared to symptomatic workers. This might indicate that high levels of specific IgG antibodies to enzymes are associated with an immune response lacking allergic manifestations in spite of IgE-mediated sensitizations to the enzymes. Atopic subjects were at greater risk of developing IgE-mediated sensitization (7/10) and allergic symptoms to enzymes (5/7). However, even without risk of atopy, IgE-mediated hypersensitivity occurred in a few subjects (3/13) exposed to enzymes by inhalation for prolonged periods of time. PMID:9298178

  12. IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults.

    Science.gov (United States)

    Kim, Sung Ryeol; Park, Hye Jung; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

    2016-08-01

    Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens. PMID:27478328

  13. The Method of Manufacturing Nonmetallic Test-Blocks on Different Sensitivity Classes

    Science.gov (United States)

    Kalinichenko, N. P.; Kalinichenko, A. N.; Lobanova, I. S.; Zaitseva, A. A.; Loboda, E. L.

    2016-01-01

    Nowadays in our modern world there is a vital question of quality control of details made from nonmetallic materials due to their wide spreading. Nondestructive penetrant testing is effective, and in some cases it is the only possible method of accidents prevention at high- risk sites. A brief review of check sample necessary for quality evaluation of penetrant materials is considered. There was offered a way of making agents for quality of penetrant materials testing according to different liquid penetrant testing sensibility classes.

  14. Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure

    Directory of Open Access Journals (Sweden)

    Neelima Mishra

    2016-01-01

    Interpretation & conclusion: Till 2012, India′s national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.

  15. Sensitive detection of botulinum neurotoxin types C and D with an immunoaffinity chromatographic column test.

    Science.gov (United States)

    Gessler, Frank; Hampe, Katrin; Böhnel, Helge

    2005-12-01

    A sensitive and specific immunoassay for the simultaneous detection of Clostridium botulinum type C (BoNT/C) and type D neurotoxin was developed. Goat anti-mouse immunoglobulin G was bound to polyethylene disks in a small disposable column used for this assay. The sample was preincubated together with monoclonal antibodies specific for the heavy chain of BoNT/C and D and affinity-purified, biotinylated polyclonal antibodies against these neurotoxins. This complex was captured on the assay disk. Streptavidin-poly-horseradish peroxidase was used as a conjugate, and a precipitating substrate allowed the direct semiquantitative readout of the assay, if necessary. For a more accurate quantitative detection, the substrate can be eluted and measured in a photometer. Depending on the preincubation time, a sensitivity of 1 mouse lethal dose ml(-1) was achieved in culture supernatants. PMID:16332765

  16. A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

    OpenAIRE

    Seth, J; Kellett, H A; G. Caldwell; Sweeting, V M; Beckett, G J; Gow, S M; Toft, A D

    1984-01-01

    The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunora...

  17. Skin Sensitive Difference of Human Body Sections under Clothing-Smirnov Test of Skin Surface Temperatures' Dynamic Changing

    Institute of Scientific and Technical Information of China (English)

    LI Jun; WU Hai-yan; WANG Yun-yi

    2004-01-01

    Skin sensitive difference of human body sections under clothing is the theoretic foundation of thermal insulation clothing design.By a new method of researching on clothing comfort perception,the skin temperature live changing procedure of human body sections affected by the same cold stimulation is inspected.Furthermore with the Smirnov test the skin temperatures dynamic changing patterns of main human body sections are obtained.

  18. A piecewise modeling approach for climate sensitivity studies: Tests with a shallow-water model

    Science.gov (United States)

    Shao, Aimei; Qiu, Chongjian; Niu, Guo-Yue

    2015-10-01

    In model-based climate sensitivity studies, model errors may grow during continuous long-term integrations in both the "reference" and "perturbed" states and hence the climate sensitivity (defined as the difference between the two states). To reduce the errors, we propose a piecewise modeling approach that splits the continuous long-term simulation into subintervals of sequential short-term simulations, and updates the modeled states through re-initialization at the end of each subinterval. In the re-initialization processes, this approach updates the reference state with analysis data and updates the perturbed states with the sum of analysis data and the difference between the perturbed and the reference states, thereby improving the credibility of the modeled climate sensitivity. We conducted a series of experiments with a shallow-water model to evaluate the advantages of the piecewise approach over the conventional continuous modeling approach. We then investigated the impacts of analysis data error and subinterval length used in the piecewise approach on the simulations of the reference and perturbed states as well as the resulting climate sensitivity. The experiments show that the piecewise approach reduces the errors produced by the conventional continuous modeling approach, more effectively when the analysis data error becomes smaller and the subinterval length is shorter. In addition, we employed a nudging assimilation technique to solve possible spin-up problems caused by re-initializations by using analysis data that contain inconsistent errors between mass and velocity. The nudging technique can effectively diminish the spin-up problem, resulting in a higher modeling skill.

  19. Photosynthesis in a test tube- dye sensitized solar cells as a teaching tool

    Energy Technology Data Exchange (ETDEWEB)

    Raturi, Atul; Fepuleai, Yoheni [Division of Physics, School of Engineering and Physics, The University of the South Pacific, Suva (Fiji)

    2010-05-15

    Dye sensitized solar cells employing natural plant dyes as phosensitizers can be effectively used to train students in the science and technology of solar cells. This is especially relevant to developing countries where facilities for silicon cell fabrication are non-existent. The cross-disciplinary nature of this device makes it very attractive for student projects. The present work describes such a project where anthocyanin dye from hibiscus flowers has been used as the electron harvester. (author)

  20. Design and tests of high sensitivity NTD Ge thermometers for the Planck-High Frequency Instrument

    OpenAIRE

    Piat, M.; Torre, J.P.; Lamarre, J. M.; Beeman, J. W.(Lawrence Berkeley National Laboratory, 94720, Berkeley, CA, USA); Bhatia, R. S.; Leriche, B.; Crussaire, J. P.; Langlet, F

    2002-01-01

    The High Frequency Instrument of Planck needs high sensitivity semi-conductors at low temperature to monitor the temperature of the bolometer plate. We have modeled such thermometers by using a semi-analytical approach of Anderson insulators, taking into account both the electrical field and the electron/phonon decoupling effects. The optimized design uses convenient NTD Ge material and has larger dimension than the initial design. The first measurements of these optimized thermometers showed...

  1. Sensitive Detection of Botulinum Neurotoxin Types C and D with an Immunoaffinity Chromatographic Column Test

    OpenAIRE

    Gessler, Frank; Hampe, Katrin; Böhnel, Helge

    2005-01-01

    A sensitive and specific immunoassay for the simultaneous detection of Clostridium botulinum type C (BoNT/C) and type D neurotoxin was developed. Goat anti-mouse immunoglobulin G was bound to polyethylene disks in a small disposable column used for this assay. The sample was preincubated together with monoclonal antibodies specific for the heavy chain of BoNT/C and D and affinity-purified, biotinylated polyclonal antibodies against these neurotoxins. This complex was captured on the assay dis...

  2. Ca2+-Transport through Plasma Membrane as a Test of Auxin Sensitivity

    Directory of Open Access Journals (Sweden)

    Anastasia A. Kirpichnikova

    2014-03-01

    Full Text Available Auxin is one of the crucial regulators of plant growth and development. The discovered auxin cytosolic receptor (TIR1 is not involved in the perception of the hormone signal at the plasma membrane. Instead, another receptor, related to the ABP1, auxin binding protein1, is supposed to be responsible for the perception at the plasma membrane. One of the fast and sensitive auxin-induced reactions is an increase of Ca2+ cytosolic concentration, which is suggested to be dependent on the activation of Ca2+ influx through the plasma membrane. This investigation was carried out with a plasmalemma enriched vesicle fraction, obtained from etiolated maize coleoptiles. The magnitude of Ca2+ efflux through the membrane vesicles was estimated according to the shift of potential dependent fluorescent dye diS-C3-(5. The obtained results showed that during coleoptiles ageing (3rd, 4th and 5th days of seedling etiolated growth the magnitude of Ca2+ efflux from inside-out vesicles was decreased. Addition of ABP1 led to a recovery of Ca2+ efflux to the level of the youngest and most sensitive cells. Moreover, the efflux was more sensitive, responding from 10−8 to 10−6 M 1-NAA, in vesicles containing ABP1, whereas native vesicles showed the highest efflux at 10−6 M 1-NAA. We suggest that auxin increases plasma membrane permeability to Ca2+ and that ABP1 is involved in modulation of this reaction.

  3. The fish embryo toxicity test as a replacement for the larval growth and survival test: A comparison of test sensitivity and identification of alternative endpoints in zebrafish and fathead minnows.

    Science.gov (United States)

    Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Stephens, Dane A; Rawlings, Jane M; Belanger, Scott E; Oris, James T

    2015-06-01

    The fish embryo toxicity (FET) test has been proposed as an alternative to the larval growth and survival (LGS) test. The objectives of the present study were to evaluate the sensitivity of the FET and LGS tests in fathead minnows (Pimephales promelas) and zebrafish (Danio rerio) and to determine if the inclusion of sublethal metrics as test endpoints could enhance test utility. In both species, LGS and FET tests were conducted using 2 simulated effluents. A comparison of median lethal concentrations determined via each test revealed significant differences between test types; however, it could not be determined which test was the least and/or most sensitive. At the conclusion of each test, developmental abnormalities and the expression of genes related to growth and toxicity were evaluated. Fathead minnows and zebrafish exposed to mock municipal wastewater-treatment plant effluent in a FET test experienced an increased incidence of pericardial edema and significant alterations in the expression of genes including insulin-like growth factors 1 and 2, heat shock protein 70, and cytochrome P4501A, suggesting that the inclusion of these endpoints could enhance test utility. The results not only show the utility of the fathead minnow FET test as a replacement for the LGS test but also provide evidence that inclusion of additional endpoints could improve the predictive power of the FET test. PMID:25929752

  4. Sensitivity of continuous performance test (CPT) at age 14years to developmental methylmercury exposure

    DEFF Research Database (Denmark)

    Julvez, Jordi; Debes, Frodi; Weihe, Pal; Choi, Anna; Grandjean, Philippe

    2010-01-01

    Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cogni...

  5. Collaborative health and enforcement operations on the quality of antimalarials and antibiotics in southeast Asia.

    Science.gov (United States)

    Yong, Yuk Lin; Plançon, Aline; Lau, Yen Hui; Hostetler, Dana M; Fernández, Facundo M; Green, Michael D; Sounvoravong, Sourisak; Nara, Suon; Boravann, Mam; Dumrong, Thitikornkovit; Bangsawan, Nurjaya; Low, Min Yong; Lim, Chin-Chin; Ai, Ruth Lee Choo; Newton, Paul N

    2015-06-01

    Counterfeit (or falsified) and substandard medicines pose a major public health risk. We describe the findings of Operation Storm I and II conducted in 2008-2009 to combat counterfeit medicines through partnership between national customs, Drug Regulatory Agencies (DRAs), and police in Cambodia, Indonesia, Laos, Myanmar, Singapore, Thailand, and Vietnam. Samples were obtained from seizures and market surveillance by national DRAs. Laboratory analysis using spectroscopic and chromatographic techniques and examination of packaging were performed. Ninety-three suspect antibiotics and 95 antimalarial samples were collected. Of the 93 antibiotics, 29 (31%) had % active pharmaceutical ingredient content (%API) 115% (including one counterfeit). Of the 95 antimalarials, 30 (32%) had %API 115% API (including one counterfeit). A significant minority of samples, antimalarials (13%) and antibiotics (15%), were collected in plastic bags with minimal or no labeling. Of 20 ampicillin samples, 13 (65%) contained medicines. PMID:25897069

  6. Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Kuhn, A; Sigges, J; Biazar, C;

    2014-01-01

    BACKGROUND: In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. OBJECTIVES: To investigate the influence of smoking on disease severity and antimalarial...... treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). METHODS: A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries....... Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. RESULTS: A high...

  7. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    OpenAIRE

    Fry, Scott R.; Michelle Meyer; Semple, Matthew G.; Cameron P Simmons; Shamala Devi Sekaran; Huang, Johnny X.; Catriona McElnea; Chang-Yi Huang; Andrea Valks; Paul R. Young; Cooper, Matthew A.

    2011-01-01

    BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early...

  8. The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

    OpenAIRE

    Fry, Scott R.; Meyer, Michelle; Semple, Matthew G.; Cameron P. Simmons; Sekaran, Shamala Devi; Johnny X. Huang; McElnea, Catriona; Huang, Chang-Yi; Valks, Andrea; Young, Paul R.; Cooper, Matthew A.

    2011-01-01

    Background Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1–9 post-onset of illness but following seroconversion it can be difficult to detect in serum. Aims To evaluate the performance of a newly developed Panbio® Dengue Early R...

  9. Bayesian integrated testing strategy (ITS) for skin sensitization potency assessment: a decision support system for quantitative weight of evidence and adaptive testing strategy.

    Science.gov (United States)

    Jaworska, Joanna S; Natsch, Andreas; Ryan, Cindy; Strickland, Judy; Ashikaga, Takao; Miyazawa, Masaaki

    2015-12-01

    The presented Bayesian network Integrated Testing Strategy (ITS-3) for skin sensitization potency assessment is a decision support system for a risk assessor that provides quantitative weight of evidence, leading to a mechanistically interpretable potency hypothesis, and formulates adaptive testing strategy for a chemical. The system was constructed with an aim to improve precision and accuracy for predicting LLNA potency beyond ITS-2 (Jaworska et al., J Appl Toxicol 33(11):1353-1364, 2013) by improving representation of chemistry and biology. Among novel elements are corrections for bioavailability both in vivo and in vitro as well as consideration of the individual assays' applicability domains in the prediction process. In ITS-3 structure, three validated alternative assays, DPRA, KeratinoSens and h-CLAT, represent first three key events of the adverse outcome pathway for skin sensitization. The skin sensitization potency prediction is provided as a probability distribution over four potency classes. The probability distribution is converted to Bayes factors to: 1) remove prediction bias introduced by the training set potency distribution and 2) express uncertainty in a quantitative manner, allowing transparent and consistent criteria to accept a prediction. The novel ITS-3 database includes 207 chemicals with a full set of in vivo and in vitro data. The accuracy for predicting LLNA outcomes on the external test set (n = 60) was as follows: hazard (two classes)-100 %, GHS potency classification (three classes)-96 %, potency (four classes)-89 %. This work demonstrates that skin sensitization potency prediction based on data from three key events, and often less, is possible, reliable over broad chemical classes and ready for practical applications. PMID:26612363

  10. Investigation of Traditional Palestinian Medicinal Plant Inula viscosa as Potential Anti-malarial Agent

    Directory of Open Access Journals (Sweden)

    M. Akkawi

    2014-10-01

    Full Text Available Malaria is a life threatening parasitic disease which is prevalent mainly in developing countries; it is the main cause of global mortality and morbidity. Development and search of novel and effective anti-malarial agents to overcome chloroquine resistance have become a very important issue. Most anti-malarial drugs target the erythrocytic stage of malaria infection, where hemozoin synthesis takes place and is considered a crucial process for the parasite survival. Throughout last decades, natural products have been a significant source of chemotherapeutics especially against malaria. Inula viscosa, Inula viscosa , is a shrub that grows around the Mediterranean basin and considered as an important Palestinian traditional medicinal herb. In this research it was found that the Palestinian flora Inula viscosa alcoholic extract has a significant and promising anti-malarial effect in both in vitro and in vivo systems. The crude alcoholic extract of Inula viscosa has the capability to impede the formation of &beta-hematin in vitro; with an efficiency of about 93% when compared to the standard chloroquine which gave 94% at comparable concentrations. in vivo studies showed that this crude extract inhibited the growth of Plasmodium parasites in the red blood cells at a rate of about 96.6%, with an EC50 value of 0.55 ng/mL. Several secondary plant metabolites may be responsible for this anti-malarial activity; the effect also may be most probably due to the presence of high concentrations of nerolidol which has often been found at high concentrationsin this plant. Nerolidol shows a stronger inhibition of hypoxanthine incorporation than quinine. Its anti-malarial effect is potentiated by other essential oils. Nerolidol is also found in several Artemisia species and in Cymbopogon citratus (lemongrass and Virola surinamensis, all plants known for their anti-malarial properties.

  11. Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

    Directory of Open Access Journals (Sweden)

    Mpimbaza Arthur

    2008-06-01

    Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

  12. Real-time hybrid model testing of floating wind turbines: sensitivity to limited actuation

    OpenAIRE

    Bachynski, Erin Elizabeth; Chabaud, Valentin Bruno; Sauder, Thomas Michel

    2015-01-01

    Real-time hybrid model testing (ReaTHM) is a new approach for conducting small-scale experimental campaign [1], [2] and [3]. In the case of a floating wind turbine in a wave basin, the aerodynamic loads on the wind turbine may be applied based on simultaneous simulations (coupled to the experiments), while the wave loads and floater response are physically tested. The objective of this paper is to demonstrate the effects of actuation limitation on the ReaTHM testing setup for a particular pla...

  13. Sensitization to Food Additives in Patients with Allergy: A Study Based on Skin Test and Open Oral Challenge.

    Science.gov (United States)

    Moghtaderi, Mozhgan; Hejrati, Zinatosadat; Dehghani, Zahra; Dehghani, Faranak; Kolahi, Niloofar

    2016-06-01

    There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy. PMID:27424134

  14. BEMUSE Phase III Report - Uncertainty and Sensitivity Analysis of the LOFT L2-5 Test

    International Nuclear Information System (INIS)

    This report summarises the various contributions (ten participants) for phase 3 of BEMUSE: Uncertainty and Sensitivity Analyses of the LOFT L2-5 experiment, a Large-Break Loss-of-Coolant-Accident (LB-LOCA). For this phase, precise requirements step by step were provided to the participants. Four main parts are defined, which are: 1. List and uncertainties of the input uncertain parameters. 2. Uncertainty analysis results. 3. Sensitivity analysis results. 4. Improved methods, assessment of the methods (optional). 5% and 95% percentiles have to be estimated for 6 output parameters, which are of two kinds: 1. Scalar output parameters (First Peak Cladding Temperature (PCT), Second Peak Cladding Temperature, Time of accumulator injection, Time of complete quenching); 2. Time trends output parameters (Maximum cladding temperature, Upper plenum pressure). The main lessons learnt from phase 3 of the BEMUSE programme are the following: - for uncertainty analysis, all the participants use a probabilistic method associated with the use of Wilks' formula, except for UNIPI with its CIAU method (Code with the Capability of Internal Assessment of Uncertainty). Use of both methods has been successfully mastered. - Compared with the experiment, the results of uncertainty analysis are good on the whole. For example, for the cladding temperature-type output parameters (1. PCT, 2. PCT, time of complete quenching, maximum cladding temperature), 8 participants out of 10 find upper and lower bounds which envelop the experimental data. - Sensitivity analysis has been successfully performed by all the participants using the probabilistic method. All the used influence measures include the range of variation of the input parameters. Synthesis tables of the most influential phenomena and parameters have been plotted and participants will be able to use them for the continuation of the BEMUSE programme

  15. Integration of pulsatile gonadotropin secretion by timed urinary measurements: an accurate and sensitive 3-hour test

    International Nuclear Information System (INIS)

    The integration of pulsatile gonadotropin secretion by the radioimmunoassay of an acetone precipitation from a short-term urine sample was evaluated. FSH and LH excretion over a 3-h period was compared to the mean level of 10 blood samples obtained every 20 min for a similar time period from 71 patients. A highly significant correlation existed between blood and urine results. In addition, the gonadotropin levels obtained from a 3-h sample correlated well with the 24-h excretion of FSH and LH from the same individual. A 3-h urine collection can provide a simple, sensitive, and accurate means of assessing circulating FSH and LH levels. (U.S.)

  16. Sensitivity and specificity of in vitro diagnostic device used for influenza rapid test in Taiwan

    Directory of Open Access Journals (Sweden)

    Kun-Teng Wang

    2014-06-01

    Full Text Available The pandemic influenza A/H1N1 outbreak resulted in 18,449 deaths in over 214 countries. In Taiwan, the influenza rapid test, an in vitro diagnostic device (Flu-IVD, only requires documented reviews for market approval by the Taiwan Food and Drug Administration. The purpose of this study was to investigate the analytical sensitivity and specificity of Flu-IVDs used in Taiwan. Analytical sensitivity and specificity tests were performed for influenza antigens A/California/7/2009 (H1N1 virus, A/Victoria/210/2009 (H3N2 virus, B/Brisbane/60/08 virus, and human coronavirus OC43. A total of seven domestic and 31 imported Flu-IVD samples were collected, of which, 20 samples had inadequate labeling, including those with removed package inserts or incorrect insert information. The analytical sensitivity of Flu-IVDs for A/H1N1, A/H3N2, and Flu B was 500–1000 ng/mL, 1000 ng/mL, and 1000 ng/mL, respectively. For the 50% cell culture infective dose (CCID50 label, the average A/H1N1 and A/H3N2 sensitivity for Flu-IVDs was log10 5.8 ± 0.5 and log10 6.6 ± 0.5 CCID50/mL, respectively. As to the specificity test, no product cross-reacted with human coronavirus OC43. This study provides important information on the Flu-IVD regulation status and can thus help the government formulate policies for the regulation of in vitro diagnostic devices in Taiwan.

  17. Sensitization to Aeroallergens in Patients with Respiratory Allergies Based on Skin-Prick Test Results

    OpenAIRE

    G Bejtullahu; Karahoda, N; H Pupovci; Lokaj-Berisha, V; Berisha, N; Lumezi, B; Ahmetaj, L

    2012-01-01

    Background: The aim of this study was to identify the most common aeroallergens in patients with asthma and rhinitis. Methods: The study enrolled 102 participants including 64 patients with respiratory allergies (among them 15 were clinically diagnosed as asthma patients, 41 with rhinitis, 8 were both) and 38 healthy controls. All of participants were subject of skin prick tests (SPT) with series of common allergenic extracts. Sera from all participants were tested for total IgE and eosinophi...

  18. Influence of rate of change of magnetization processes on sensitivity of magnetic adaptive testing

    Czech Academy of Sciences Publication Activity Database

    Tomáš, Ivan; Vértesy, G.; Kadlecová, Jana

    2009-01-01

    Roč. 321, č. 8 (2009), s. 1019-1024. ISSN 0304-8853 R&D Projects: GA AV ČR 1QS100100508 Grant ostatní: HSRF(HU) K-62466 Institutional research plan: CEZ:AV0Z10100520 Keywords : magnetic adaptive testing * nondestructive testing * ferromagnetic materials Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.204, year: 2009

  19. Are somatosensory evoked potentials of the tibial nerve the most sensitive test in diagnosing multiple sclerosis?

    OpenAIRE

    Djuric S; Djuric V; Zivkovic M; Milosevic V; Jolic M; Stamenovic J; Djordjevic G.; Calixto M

    2010-01-01

    Background : Multiple sclerosis (MS) is mostly diagnosed clinically, but the diagnosis has significantly improved through the use of brain magnetic resonance imaging (MRI), testing of cerebrospinal fluid, and multimodal evoked potentials (MEPs). Even though MRI is the superior method in diagnosing this illness, MEPs remain important because they can detect clinically silent lesions in the sensory and motor pathways of the central nervous system (CNS). Aim : The aim of the study is to test the...

  20. Radiorespirometric testing of antibiotic sensitivity in urinary tract infections: concise communication

    International Nuclear Information System (INIS)

    A radiometric method, based on inhibition of 14CO2 release from bacterial metabolism of C-14-labeled glucose, was applied to test the susceptibility of urinary organisms to antibiotics. The testing was also carried out by the routine disc diffusion method after isolation of the organisms. Results of susceptibility to antibiotics could be obtained within 2 to 4 hr by the radiometric technique, compared with the 48 hr required for the disc method

  1. Aluminum sulfate significantly reduces the skin test response to common allergens in sensitized patients

    Directory of Open Access Journals (Sweden)

    Grier Thomas J

    2006-02-01

    Full Text Available Abstract Background Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens. Methods Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study. Results Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated. Conclusion Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen.

  2. Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication

    OpenAIRE

    Oguariri, Raphael M.; Joseph W Adelsberger; Michael W Baseler; Imamichi, Tomozumi

    2010-01-01

    Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia. Here we investigated the impact of PYR and two other clinical anti-malarial drugs (chloroquine [CQ] or artemisinin [ART]) on HIV-1 replication. Peripheral blood mononuclear cells (PBMCs) or MT-2 cells were infected with HIVNL4.3 strain and treated with different concentrations of the anti-malarial drugs. HIV-1 replication was measured using p24 ELISA. We show that 10 μM...

  3. Childhood maltreatment, 9/11 exposure, and latent dimensions of psychopathology: A test of stress sensitization

    Science.gov (United States)

    Meyers, Jacquelyn L.; Lowe, Sarah R.; Eaton, Nicholas R.; Krueger, Robert; Grant, Bridget F.; Hasin, Deborah

    2015-01-01

    On September 11, 2001, a terrorist attack occurred in the U.S. (9/11). Research on 9/11 and psychiatric outcomes has focused on individual disorders rather than the broader internalizing (INT) and externalizing (EXT) domains of psychopathology, leaving unknown whether direct and indirect 9/11 exposure differentially impacted these domains rather than individual disorders. Further, whether such effects were exacerbated by earlier childhood maltreatment (i.e. stress sensitization) is unknown. 18,713 participants from a U.S. national sample with no history of psychiatric disorders prior to 9/11 were assessed using a structured in-person interview. Structural equation modeling conducted in a sample who endorsed no psychiatric history prior to 9/11, indicated that indirect exposure to 9/11 (i.e. media, friends/family) was related to both EXT (alcohol, nicotine, and cannabis dependence, and antisocial personality disorder) and INT (major depression, generalized anxiety, and post-traumatic stress disorder (PTSD)) dimensions of psychopathology (EXT: β = 0.10, p 9/11 was exacerbated (Interactions: β = 0.06, p 9/11 impacted latent liability to broad domains of psychopathology in the US general population rather than specific disorders with the exception of PTSD, which had independent effects beyond INT (as indicated by a significant (p < 0.05) improvement in modification indices). Findings also indicated that childhood maltreatment increases the risk associated with adult trauma exposure, providing further evidence for the concept of stress sensitization. PMID:26037889

  4. Gravity wave and neutrino bursts from stellar collapse: A sensitive test of neutrino masses

    International Nuclear Information System (INIS)

    New methods are proposed with the goal to determine absolute neutrino masses from the simultaneous observation of the bursts of neutrinos and gravitational waves emitted during a stellar collapse. It is shown that the neutronization electron neutrino flash and the maximum amplitude of the gravitational wave signal are tightly synchronized with the bounce occurring at the end of the core collapse on a time scale better than 1 ms. The existing underground neutrino detectors (SuperKamiokande, SNO,...) and the gravity wave antennas soon to operate (LIGO, VIRGO,...) are well matched in their performance for detecting galactic supernovae and for making use of the proposed approach. Several methods are described, which apply to the different scenarios depending on neutrino mixing. Given the present knowledge on neutrino oscillations, the methods proposed are sensitive to a mass range where neutrinos would essentially be mass degenerate. The 95% C.L. upper limit which can be achieved varies from 0.75 eV/c2 for large νe survival probabilities to 1.1 eV/c2 when in practice all νe's convert into νμ's or ντ's. The sensitivity is nearly independent of the supernova distance

  5. A Novel High Sensitivity Sensor for Remote Field Eddy Current Non-Destructive Testing Based on Orthogonal Magnetic Field

    Directory of Open Access Journals (Sweden)

    Xiaojie Xu

    2014-12-01

    Full Text Available Remote field eddy current is an effective non-destructive testing method for ferromagnetic tubular structures. In view of conventional sensors’ disadvantages such as low signal-to-noise ratio and poor sensitivity to axial cracks, a novel high sensitivity sensor based on orthogonal magnetic field excitation is proposed. Firstly, through a three-dimensional finite element simulation, the remote field effect under orthogonal magnetic field excitation is determined, and an appropriate configuration which can generate an orthogonal magnetic field for a tubular structure is developed. Secondly, optimized selection of key parameters such as frequency, exciting currents and shielding modes is analyzed in detail, and different types of pick-up coils, including a new self-differential mode pick-up coil, are designed and analyzed. Lastly, the proposed sensor is verified experimentally by various types of defects manufactured on a section of a ferromagnetic tube. Experimental results show that the proposed novel sensor can largely improve the sensitivity of defect detection, especially for axial crack whose depth is less than 40% wall thickness, which are very difficult to detect and identify by conventional sensors. Another noteworthy advantage of the proposed sensor is that it has almost equal sensitivity to various types of defects, when a self-differential mode pick-up coil is adopted.

  6. Pyrotechnic hazards classification and evaluation program. Phase 3, segments 1-4: Investigation of sensitivity test methods and procedures for pyrotechnic hazards evaluation and classification, part A

    Science.gov (United States)

    1971-01-01

    The findings, conclusions, and recommendations relative to the investigations conducted to evaluate tests for classifying pyrotechnic materials and end items as to their hazard potential are presented. Information required to establish an applicable means of determining the potential hazards of pyrotechnics is described. Hazard evaluations are based on the peak overpressure or impulse resulting from the explosion as a function of distance from the source. Other hazard classification tests include dust ignition sensitivity, impact ignition sensitivity, spark ignition sensitivity, and differential thermal analysis.

  7. Sensitive and Quantitative Detection of C-Reaction Protein Based on Immunofluorescent Nanospheres Coupled with Lateral Flow Test Strip.

    Science.gov (United States)

    Hu, Jiao; Zhang, Zhi-Ling; Wen, Cong-Ying; Tang, Man; Wu, Ling-Ling; Liu, Cui; Zhu, Lian; Pang, Dai-Wen

    2016-06-21

    Sensitive and quantitative detection of protein biomarkers with a point-of-care (POC) assay is significant for early diagnosis, treatment, and prognosis of diseases. In this paper, a quantitative lateral flow assay with high sensitivity for protein biomarkers was established by utilizing fluorescent nanospheres (FNs) as reporters. Each fluorescent nanosphere (FN) contains 332 ± 8 CdSe/ZnS quantum dots (QDs), leading to its superstrong luminescence, 380-fold higher than that of one QD. Then a detection limit of 27.8 pM C-reaction protein (CRP) could be achieved with an immunofluorescent nanosphere (IFN)-based lateral flow test strip. The assay was 257-fold more sensitive than that with a conventional Au-based lateral flow test strip for CRP detection. Besides, the fluorescence intensity of FNs and bioactivity of IFNs were stable during 6 months of storage. Hence, the assay owns good reproducibility (intra-assay variability of 5.3% and interassay variability of 6.6%). Furthermore, other cancer biomarkers (PSA, CEA, AFP) showed negative results by this method, validating the excellent specificity of the method. Then the assay was successfully applied to quantitatively detect CRP in peripheral blood plasma samples from lung cancer and breast cancer patients, and healthy people, facilitating the diagnosis of lung cancer. It holds a good prospect of POC protein biomarker detection. PMID:27253137

  8. Treatment of Polymicrobial Osteomyelitis with Ceftolozane-Tazobactam: Case Report and Sensitivity Testing of Isolates.

    Science.gov (United States)

    Jolliff, Jeffrey C; Ho, Jackie; Joson, Jeremiah; Heidari, Arash; Johnson, Royce

    2016-01-01

    Stenotrophomonas maltophilia is an inherently multidrug resistant (MDR) opportunistic pathogen with many mechanisms of resistance. SENTRY studies reveal decreasing sensitivities of S. maltophilia to trimethoprim-sulfamethoxazole and fluoroquinolones. Ceftolozane-tazobactam (Zerbaxa, Merck & Co., Inc.) a novel intravenous combination agent of a third-generation cephalosporin and β-lactamase inhibitor was demonstrated to have in vitro activity against many Gram-positive, Gram-negative, and MDR organisms. Data for ceftolozane-tazobactam's use outside of Food and Drug Administration (FDA) approved indications has been limited thus far to two case reports which demonstrated its efficacy in pan-resistant Pseudomonas aeruginosa pneumonia. Herein, we describe the first published case of treatment of MDR S. maltophilia in polymicrobial osteomyelitis with long-term (>14 days) ceftolozane-tazobactam and metronidazole. Ceftolozane-tazobactam may offer a possible alternative for clinicians faced with limited options in the treatment of resistant pathogens including MDR S. maltophilia. PMID:27437155

  9. FUDGE: A Program for Performing Nuclear Data Testing and Sensitivity Studies

    International Nuclear Information System (INIS)

    We have developed a program called FUDGE that allows one to modify data from LLNL's nuclear database. After modifying data, FUDGE can then be instructed to process the data into the formats used by LLNL's deterministic (ndf) and the Monte Carlo (MCAPM) transport codes. This capability allows users to perform nuclear data sensitivity studies without modification of the transport modeling codes. FUDGE is designed to be user friendly (object-oriented) and fast (the modification and processing typically takes about a minute). It uses Python as a front-end, making it flexible and scriptable. Comparing, plotting, and printing of the data are also supported. An overview of FUDGE will be presented as well as examples

  10. Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria

    Directory of Open Access Journals (Sweden)

    Uzochukwu Benjamin

    2009-02-01

    Full Text Available Abstract Background There is little existing knowledge about actual quality of drugs provided by different providers in Nigeria and in many sub-Saharan African countries. Such information is important for improving malaria treatment that will help in the development and implementation of actions designed to improve the quality of treatment. The objective of the study was to determine the quality of drugs used for the treatment of malaria in a broad spectrum of public and private healthcare providers. Methods The study was undertaken in six towns (three urban and three rural in Anambra state, south-east Nigeria. Anti-malarials (225 samples, which included artesunate, dihydroartemisinin, sulphadoxine-pyrimethamine (SP, quinine, and chloroquine, were either purchased or collected from randomly selected providers. The quality of these drugs was assessed by laboratory analysis of the dissolution profile using published pharmacopoeial monograms and measuring the amount of active ingredient using high performance liquid chromatography (HPLC. Findings It was found that 60 (37% of the anti-malarials tested did not meet the United States Pharmacopoeia (USP specifications for the amount of active ingredients, with the suspect drugs either lacking the active ingredients or containing suboptimal quantities of the active ingredients. Quinine (46% and SP formulations (39% were among drugs that did not satisfy the tolerance limits published in USP monograms. A total of 78% of the suspect drugs were from private facilities, mostly low-level providers, such as patent medicine dealers (vendors. Conclusion This study found that there was a high prevalence of poor quality drugs. The findings provide areas for public intervention to improve the quality of malaria treatment services. There should be enforced checks and regulation of drug supply management as well as stiffer penalties for people stocking substandard and counterfeit drugs.

  11. Childhood maltreatment, 9/11 exposure, and latent dimensions of psychopathology: A test of stress sensitization.

    Science.gov (United States)

    Meyers, Jacquelyn L; Lowe, Sarah R; Eaton, Nicholas R; Krueger, Robert; Grant, Bridget F; Hasin, Deborah

    2015-09-01

    On September 11, 2001, a terrorist attack occurred in the U.S. (9/11). Research on 9/11 and psychiatric outcomes has focused on individual disorders rather than the broader internalizing (INT) and externalizing (EXT) domains of psychopathology, leaving unknown whether direct and indirect 9/11 exposure differentially impacted these domains rather than individual disorders. Further, whether such effects were exacerbated by earlier childhood maltreatment (i.e. stress sensitization) is unknown. 18,713 participants from a U.S. national sample with no history of psychiatric disorders prior to 9/11 were assessed using a structured in-person interview. Structural equation modeling conducted in a sample who endorsed no psychiatric history prior to 9/11, indicated that indirect exposure to 9/11 (i.e. media, friends/family) was related to both EXT (alcohol, nicotine, and cannabis dependence, and antisocial personality disorder) and INT (major depression, generalized anxiety, and post-traumatic stress disorder (PTSD)) dimensions of psychopathology (EXT: β = 0.10, p < 0.001; INT: β = 0.11, p < 0.001) whereas direct exposure was associated with the INT dimension only (β = 0.11, p < 0.001). For individuals who had experienced childhood maltreatment, the risk for EXT and INT dimensions associated with 9/11 was exacerbated (Interactions: β = 0.06, p < 0.01; β = 0.07, p < 0.001, respectively). These findings indicate that 9/11 impacted latent liability to broad domains of psychopathology in the US general population rather than specific disorders with the exception of PTSD, which had independent effects beyond INT (as indicated by a significant (p < 0.05) improvement in modification indices). Findings also indicated that childhood maltreatment increases the risk associated with adult trauma exposure, providing further evidence for the concept of stress sensitization. PMID:26037889

  12. Hemoglobin interactions with αB crystallin: a direct test of sensitivity to protein instability.

    Directory of Open Access Journals (Sweden)

    Tyler J W Clark

    Full Text Available As a small stress response protein, human αB crystallin, detects protein destabilization that can alter structure and function to cause self assembly of fibrils or aggregates in diseases of aging. The sensitivity of αB crystallin to protein instability was evaluated using wild-type hemoglobin (HbA and hemoglobin S (HbS, the glutamate-6-valine mutant that forms elongated, filamentous aggregates in sickling red blood cells. The progressive thermal unfolding and aggregation of HbA and HbS in solution at 37°C, 50°C and 55°C was measured as increased light scattering. UV circular dichroism (UVCD was used to evaluate conformational changes in HbA and HbS with time at the selected temperatures. The changes in interactions between αB crystallin and HbA or HbS with temperature were analyzed using differential centrifugation and SDS PAGE at 37°C, 50°C and 55°C. After only 5 minutes at the selected temperatures, differences in the aggregation or conformation of HbA and HbS were not observed, but αB crystallin bound approximately 6% and 25% more HbS than HbA at 37°C, and 50°C respectively. The results confirmed (a the remarkable sensitivity of αB crystallin to structural instabilities at the very earliest stages of thermal unfolding and (b an ability to distinguish the self assembling mutant form of HbS from the wild type HbA in solution.

  13. Exploring Population Sensitivity of Linking Functions across Three Law School Admission Test Administrations

    Science.gov (United States)

    Liu, Mei; Holland, Paul W.

    2008-01-01

    The simplified version of the Dorans and Holland (2000) measure of population invariance, the root mean square difference (RMSD), is used to explore the degree of dependence of linking functions on the Law School Admission Test (LSAT) subpopulations defined by examinees' gender, ethnic background, geographic region, law school application status,…

  14. Testing taste sensitivity and aversion in very young children : development of a procedure

    NARCIS (Netherlands)

    Visser, J; Kroeze, J.H.A.; Kamps, WA; Bijleveld, CMA

    2000-01-01

    Taste perception in 45 3- to 6-year-old children was tested using procedures specifically designed for this age group. Detection thresholds for sucrose and urea were measured by a staircase method and aversion to urea was assessed hedonically, using drawings of facial expressions. All children under

  15. The optimal patch test concentration for ascaridole as a sensitizing component of tea tree oil

    NARCIS (Netherlands)

    Christoffers, Wietske Andrea; Bloemeke, Brunhilde; Coenraads, Pieter-Jan; Schuttelaar, Marie-Louise Anna

    2014-01-01

    BACKGROUND: Tea tree oil is used as a natural remedy, but is also a popular ingredient in household and cosmetic products. Oxidation of tea tree oil results in degradation products, such as ascaridole, which may cause allergic contact dermatitis. OBJECTIVES: To identify the optimal patch test concen

  16. Mind the gaps - the epidemiology of poor-quality anti-malarials in the malarious world - analysis of the WorldWide Antimalarial Resistance Network database

    OpenAIRE

    Tabernero, Patricia; Facundo M Fernández; Green, Michael; Guerin, Philippe J; Newton, Paul N.

    2014-01-01

    Background Poor quality medicines threaten the lives of millions of patients and are alarmingly common in many parts of the world. Nevertheless, the global extent of the problem remains unknown. Accurate estimates of the epidemiology of poor quality medicines are sparse and are influenced by sampling methodology and diverse chemical analysis techniques. In order to understand the existing data, the Antimalarial Quality Scientific Group at WWARN built a comprehensive, open-access, global datab...

  17. Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs

    OpenAIRE

    Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F.; Christoffels, Alan

    2016-01-01

    Background A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Methods Natural products with in vitro antiplasmodial activities (NAA) we...

  18. Combination of resonance integral and Maxwellian 30 keV data – A sensitive test of the resonance region

    International Nuclear Information System (INIS)

    Highlights: ► Neutron-induced capture cross sections can be tested by considering the Resonance Integral and Maxwellian average cross section at 30 keV. ► Results are presented for typical reactions from EAF-2010 and ENDF/B-VII.1. ► Including data at the energies of 14.5 MeV and 0.0253 eV as well as the spontaneous fission spectrum of 252-Cf improve the validation process. ► Examples where capture reactions can be improved by this validation procedure are presented. -- Abstract: This paper presents the approach of a combined use of resonance integrals and average Maxwellian cross sections (MACS) at kT = 30 keV to test and validate the resolved resonance range or its reconstructed cross section curve. Based on these two integral measurements a sensitive and energy dependent test can be provided. These two integral quantities cover with their neutron spectra the energy region between En = 0.5 eV up to several hundred keV, respectively, with different weighting. Our principal motivation is to produce a validation tool, sensitive to the lower and upper parts of the resonance region through the difference in the applied 1/E and kT = 30 keV Maxwell–Boltzmann spectra of the resonance integral and MACS data

  19. Examination of sensitivity and specificity of some serological tests in diagnostics of bovine brucellosis

    OpenAIRE

    Matović Kazimir; Ašanin Ružica; Radojičić Sonja; Lako B.; Žarković A.

    2008-01-01

    The most reliable diagnosis of an infectuous disease is confirmed by isolation of its pathogen. When it comes to brucellosis, it is important to know that brucella isolation is rarely successful; it is not only very complicated but is as well hazardous for laboratory workers. Due to the above mentioned reasons, it is reasonable to use serological tests for routine diagnosis of this zoonose. This paper deals with examination of bovine sera samples with the aim to detect the titer of specific a...

  20. What is the most sensitive measure of water maze probe test performance?

    Directory of Open Access Journals (Sweden)

    Kirill Zaslavsky

    2009-03-01

    Full Text Available The water maze is commonly used to assay spatial cognition, or, more generally, learning and memory in experimental rodent models. In the water maze, mice or rats are trained to navigate to a platform located below the water’s surface. Spatial learning is then typically assessed in a probe test, where the platform is removed from the pool and the mouse or rat is allowed to search for it. Performance in the probe test may then be evaluated using either occupancy-based (percent time in virtual quadrant [Q] or zone [Z] centered on former platform location, error-based (mean proximity to former platform location [P] or counting-based (platform crossings [X] measures. While these measures differ in their popularity, whether they differ in their ability to detect group differences is not known. To address this question we compiled 5 separate databases, containing more than 1600 mouse probe tests. Random selection of individual trials from respective databases then allowed us to simulate experiments with varying sample and effect sizes. Using this Monte Carlo-based method, we found that the P measure consistently outperformed the Q, Z and X measures in its ability to detect group differences. This was the case regardless of sample or effect size, and using both parametric and non-parametric statistical analyses. The relative superiority of P over other commonly used measures suggests that it is the most appropriate measure to employ in both low- and high-throughput water maze screens.

  1. Assessment of hydrogen cracking sensitivity of interfaces in welds between stainless and low alloy steels by a tensile separation test

    International Nuclear Information System (INIS)

    In PWR the primary coolant circuit is coated with 23 CN 20-10 and intermediary alloys are used for welds between main components (pressure vessel, steam generators, pressurizers) made of low alloy steels and stainless steel pipes. After description of the chemical and structural particularities of the bonding zone and evidencing of the interface sensitivity to H2 induced cracking, the paper presents the implementation of the tensile shearing test: preparation, procedure, evaluation, results achieved. The prominent role of the stress relief treatment is highlighted

  2. Antimalarial qinghaosu/artemisinin: The therapy worthy of a Nobel Prize

    Directory of Open Access Journals (Sweden)

    Jerapan Krungkrai

    2016-05-01

    Full Text Available Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.

  3. Antimalarial qinghaosu/artemisinin:The therapy worthy of a Nobel Prize

    Institute of Scientific and Technical Information of China (English)

    Jerapan Krungkrai

    2016-01-01

    Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.

  4. A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity

    Directory of Open Access Journals (Sweden)

    Cleydson Breno R. Santos

    2013-12-01

    Full Text Available The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs and molecular docking were used to investigate the interaction between ligands and the receptor (heme. Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE, the charge on the O11 oxygen atom (QO11, the torsion angle O1-O2-Fe-N2 (D2 and the maximum rate of R/Sanderson Electronegativity (RTe+. These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents.

  5. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity

    OpenAIRE

    Rijpma, S.R.; Heuvel, J. J.; van de Velden, M.; Sauerwein, R. W.; Russel, F. G.; Koenderink, J.B.

    2014-01-01

    BACKGROUND: Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involved in drug deposition, as they are located at membranes of many uptake and excretory organs and at protective barriers, where they export endogenous and xenobiotic compounds, including pharmaceutica...

  6. New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica

    DEFF Research Database (Denmark)

    Valsaraj, R; Pushpangadan, P; Smitt, U W;

    1997-01-01

    A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-......, antimalarial, and antifungal activity in vitro....

  7. Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Leslie Toby

    2008-12-01

    Full Text Available Abstract Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities.

  8. Selenomethionine Uptake Test as a Sensitive Indicator of Placental Function in the Last Trimester of Pregnancy

    International Nuclear Information System (INIS)

    During the last trimester of pregnancy the demands of the human foetus for nutrients can only just be met by the normal placenta. If the placenta is damaged or poorly developed foetal growth is impaired or, in severe cases, the baby dies. It is clinically important to detect placental failure as early as possible so that the underlying cause can be treated, or if this is not possible the baby can be delivered before term. 75Se-selenomethionine is one of the amino-acids which is taken up by the placenta from the mother's blood and actively transported against a concentration gradient to the foetus. In the selenomethionine uptake test two 3-in. diameter Nal detectors in cylindrical collimators are used; one is positioned over the mother's mediastinum and the other over her uterus. The output from each detector is fed through a pulse-height analyser to a recording ratemeter. A dose of 2 μCi of selenomethionine is given intravenously to the mother, and from the recorded count-rates during the next 15 minutes the efficiency of placental amino-acid transport can be assessed. The maximum radiation dose to the mother or foetus is 20 mrad. This test has been applied without ill effects to over 500 patients in whom there were clinical grounds for suspecting placental damage. Gross placental failure and intrauterine death were invariably associated with a very low selenomethionine-uptake over the uterus, and high uterine uptakes were always associated with good placental function. Misleading results may be obtained in cases with rhesus immunization or congenital defect in the foetus, since in such cases foetal growth failure is not due to a defect of transport in the placenta. Generally the test provides a quick, simple and reliable indication of the nutritive function of the placenta, and can be safely used to select those mothers who need particularly careful clinical management. (author)

  9. Design, Fabrication and Temperature Sensitivity Testing of a Miniature Piezoelectric-Based Sensor for Current Measurements

    Directory of Open Access Journals (Sweden)

    Steven B. Lao

    2014-07-01

    Full Text Available Grid capacity, reliability, and efficient distribution of power have been major challenges for traditional power grids in the past few years. Reliable and efficient distribution within these power grids will continue to depend on the development of lighter and more efficient sensing units with lower costs in order to measure current and detect failures across the grid. The objective of this paper is to present the development of a miniature piezoelectric-based sensor for AC current measurements in single conductors, which are used in power transmission lines. Additionally presented in this paper are the thermal testing results for the sensor to assess its robustness for various operating temperatures.

  10. Investigating 13C +12C reaction by the activation method. Sensitivity tests

    Science.gov (United States)

    Chesneanu, Daniela; Trache, L.; Margineanu, R.; Pantelica, A.; Ghita, D.; Straticiuc, M.; Burducea, I.; Blebea-Apostu, A. M.; Gomoiu, C. M.; Tang, X.

    2015-02-01

    We have performed experiments to check the limits of sensitivity of the activation method using the new 3 MV Tandetron accelerator and the low and ultra-low background laboratories of the "Horia Hulubei" National Institute of Physics and Nuclear Engineering (IFIN-HH). We have used the 12C +13C reaction at beam energies Elab= 6, 7 and 8 MeV. The knowledge of this fusion cross section at deep sub-barrier energies is of interest for astrophysical applications, as it provides an upper limit for the fusion cross section of 12C +12C over a wide energy range. A 13C beam with intensities 0.5-2 particleμA was provided by the accelerator and used to bombard graphite targets, resulting in activation with 24Na from the 12C (13C ,p) reaction. The 1369 and 2754 keV gamma-rays from 24Na de-activation were clearly observed in the spectra obtained in two different laboratories used for measurements at low and ultralow background: one at the surface and one located underground in the Unirea salt mine from Slanic Prahova, Romania. In the underground laboratory, for Elab = 6 MeV we have measured an activity of 0.085 ± 0.011 Bq, corresponding to cross sections of 1-3 nb. This demonstrates that it is possible to measure 12C targets irradiated at lower energies for at least 10 times lower cross sections than before β-γ coincidences will lead us another factor of 10 lower, proving that this installations can be successfully used for nuclear astrophysics measurements.

  11. Spanish Round Robin test on water sensitivity test of bituminous mixtures; Ejercicio espanol interlaboratorios sobre el ensayo de sensibilidad al gua de mezclas bituminosas

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Saez, R.; Enrique Gabeiras, L.; Miranda Perez, L.; Valor Hernandez, F.

    2011-07-01

    The amendment of Article 542 and 543 on the hot asphalt mixtures included in the Spanish Technical specifications for Road Construction (PG-3), by Circular Order 24/2008, introduced a new series of modification to adapt Spanish regulations to European standards series EN 13108. Among the various amendments, new tests methods and design criteria are considered, as UNE-EN 12697-12 for assessing the water sensitivity on compacted specimens, which is mandatory for every kind of bituminous mixture. In this paper, firstly a comparison between the European method and the old Spanish method described in the NLT-162 is made, explaining the experimental conditions selected. The results of an interlaboratory study or Round Robin Test conducted in ten Spanish laboratories are subsequently described and analyzed, in order to allow each laboratory to assess its technical performance, and also to determine quantitatively the precision of the new method in terms of repeatability and reproducibility. (Author) 15 refs.

  12. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

    Directory of Open Access Journals (Sweden)

    Shen S

    2015-06-01

    Full Text Available Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data

  13. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

    Directory of Open Access Journals (Sweden)

    Lee Sue J

    2009-11-01

    Full Text Available Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. Methods The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. Results Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. Conclusion Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women. Patients with

  14. Predicted Sensitivity for Tests of Short-range Gravity with a Novel Parallel-plate Torsion Pendulum

    Science.gov (United States)

    Richards, Matthew; Baxley, Brandon; Hoyle, C. D.; Leopardi, Holly; Shook, David

    2011-11-01

    The parallel-plate torsion pendulum apparatus at Humboldt State University is designed to test the Weak Equivalence Principle (WEP) and the gravitational inverse-square law (ISL) of General Relativity at unprecedented levels in the sub-millimeter regime. Some versions of String Theory predict additional dimensions that might affect the gravitational inverse-square law (ISL) at sub-millimeter levels. Some models also predict the existence of unobserved subatomic particles, which if exist, could cause a violation in the WEP at short distances. Short-range tests of gravity and the WEP are also instrumental in investigating possible proposed mechanisms that attempt to explain the accelerated expansion of the universe, generally attributed to Dark Energy. The weakness of the gravitational force makes measurement very difficult at small scales. Testing such a minimal force requires highly isolated experimental systems and precise measurement and control instrumentation. Moreover, a dedicated test of the WEP has not been performed below the millimeter scale. This talk will discuss the improved sensitivity that we expect to achieve in short-range gravity tests with respect to previous efforts that employ different experimental configurations.

  15. ONE-DIMENSIONAL TIME TO EXPLOSION (THERMAL SENSITIVITY) TESTS ON PETN, PBX-9407, LX-10, AND LX-17

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Strout, Steve [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); McClelland, Matthew [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ellsworth, Fred Ellsworth [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-01-28

    Incidents caused by fire and combat operations can heat energetic materials that may lead to thermal explosion and result in structural damage and casualty. Some explosives may thermally explode at fairly low temperatures (< 100 C) and the violence from thermal explosion may cause a significant damage. Thus it is important to understand the response of energetic materials to thermal insults. The One Dimensional Time to Explosion (ODTX) system at the Lawrence Livermore National Laboratory has been used for decades to measure times to thermal explosion, threshold thermal explosion temperature, and determine the kinetic parameters of thermal decomposition of energetic materials. Samples of different configurations (pressed part, powder, paste, and liquid) can be tested in the system. The ODTX testing can also provide useful data for assessing the thermal explosion violence of energetic materials. This report summarizes the results of our recent ODTX experiments on PETN powder, PBX-9407 pressed part, LX-10 pressed part, LX-17 pressed part and compares the test data that were obtained decades ago with the older version of ODTX system. Test results show the thermal sensitivity of various materials tested in the following order: PETN> PBX-9407 > LX-10 > LX-17.

  16. Sensitivity is not an intrinsic property of a diagnostic test: empirical evidence from histological diagnosis of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Carrilho Carla

    2009-12-01

    Full Text Available Abstract Background We aimed to provide empirical evidence of how spectrum effects can affect the sensitivity of histological assessment of Helicobacter pylori infection, which may contribute to explain the heterogeneity in prevalence estimates across populations with expectedly similar prevalence. Methods Cross-sectional evaluation of dyspeptic subjects undergoing upper digestive endoscopy, including collection of biopsy specimens from the greater curvature of the antrum for assessment of H. pylori infection by histopathological study and polymerase chain reaction (PCR, from Portugal (n = 106 and Mozambique (n = 102 following the same standardized protocol. Results In the Portuguese sample the prevalence of infection was 95.3% by histological assessment and 98.1% by PCR. In the Mozambican sample the prevalence was 63.7% and 93.1%, respectively. Among those classified as infected by PCR, the sensitivity of histological assessment was 96.2% among the Portuguese and 66.3% among the Mozambican. Among those testing positive by both methods, 5.0% of the Portuguese and 20.6% of the Mozambican had mild density of colonization. Conclusions This study shows a lower sensitivity of histological assessment of H. pylori infection in Mozambican dyspeptic patients compared to the Portuguese, which may be explained by differences in the density of colonization, and may contribute to explain the heterogeneity in prevalence estimates across African settings.

  17. A capacitive DNA sensor-based test for simple and sensitive analysis of antibiotic resistance in field setting.

    Science.gov (United States)

    Liu, Yanling; Hedström, Martin; Chen, Dongfeng; Fan, Xiaolong; Mattiasson, Bo

    2015-02-15

    To meet urgent needs for solving serious worldwide drug-resistance problems, a sensitive label-free capacitive sensor developed in our group was investigated as a tool to be applied in the field of antibiotic resistance genotyping, for instance the detection of ampicillin resistance gene (ampR). Proof-of-concept data demonstrated its detection sensitivity of pico-molar without any signal amplification step and a dynamic range of at least three orders of magnitude. The detection limits of less than 1 pM for the single-stranded ampR oligonucleotide and 4 pM for the double-stranded target can reliably be achieved after only 2.5 min sample reaction. Reusability of the probe-functionalized disposable electrode was investigated by comparing different regeneration solutions; mix of 25 mM NaOH/30% formamide was employed to regenerate the electrode for at least six cycles without significant loss of sensing ability. Assay is performed automatically and result is retrieved in 20 min. The developed sensitive genotyping tool is expected to provide simple, fast and affordable screening for monitoring spread of antibiotic resistances, which is suitable for testing in field setting. PMID:25238540

  18. Experimental Investigation of the Cross-Sensitivity and Size Effects of Polyvinylidene Fluoride Film Sensors on Modal Testing

    Directory of Open Access Journals (Sweden)

    Kuo-Chih Chuang

    2012-12-01

    Full Text Available Due to advantages such as light weight, flexibility, and low cost, polyvinylidene fluoride (PVDF films have been widely used in engineering applications as sensors for detecting strain, pressure, or micro-force. However, it is known that PVDF strain sensors have strain cross-sensitivity in mutually orthogonal directions. Furthermore, the size of the PVDF film sensor would also affect the dynamic strain sensing performance. In this paper, to investigate the cross-sensitivity and size effects experimentally, we employ PVDF film sensors to perform dynamic measurements on a cantilever beam. Since the vibrations of the cantilever beam are excited by impacts of a steel ball, the induced highly repeatable transient responses contain a wide range of resonant frequencies and thus can be used to investigate both the size and cross-sensitivity effects of the PVDF film sensors in a dynamic sensing environment. Based on the experimental results of the identified resonant frequencies compared with results obtained from a strain gauge, finite element calculations, and theoretical predictions, suggestions for the use of the PVDF strain sensor in modal testing are given in this paper.

  19. High-sensitivity crossed-resonator laser apparatus for improved tests of Lorentz invariance and of space-time fluctuations

    Science.gov (United States)

    Chen, Q.; Magoulakis, E.; Schiller, S.

    2016-01-01

    We describe an improved Michelson-Morley-type laser apparatus for highly sensitive tests of Lorentz invariance in the electron and photon sectors. The realization of an ultrastable rotation table reduced by more than one order systematic effects occurring with the rotation period. We also reduced by one order the noise level, resulting in integration times smaller by more than one order. Under reasonable assumptions, we determine five coefficients of the standard model extension test theory, with uncertainties similar to the previous best experiments, but with a 30 times shorter data acquisition time span. Four coefficients are consistent with zero at the (4 - 8 )×10-18 level, while one, (κ˜ e -)Z Z≃5 ×10-17 , appears to be caused by unidentified systematic effects. In addition, the apparatus' performance leads to a limit for the strength of (hypothetical) space-time fluctuations improved by a factor of 3.7.

  20. Structural analysis, manufacturing and test evaluation of a polarization sensitive reflector

    Science.gov (United States)

    Weiss, W.; Pfeifer, K.; Leitner, R.

    1986-02-01

    A parabolic reflector for space applications was developed. The reflector consists of two Kevlar/Nomex sandwich shells with a diameter of 1100 mm. Their edges are connected by a Kevlar/glass ring. The rear shell is fixed to the satellite by a conical carbon fiber composite cylinder and stiffened by four Kevlar/Nomex ribs. To minimize the thermal stresses the thermal expansion coefficients were adjusted to the reflector shells. In the static analysis a finite element calculation was performed for an acceleration of 15 g and for the most critical Sun irradiation with a partly shadowed reflector. All stresses are below the strength limits. The antenna was tested by sine vibration, acoustic noise, thermal cycling, and solar simulation without failure.

  1. Portable penetrometer for agricultural soil: sensitivity test to identify critical compaction depth

    Directory of Open Access Journals (Sweden)

    João Carlos Medeiros

    2010-12-01

    Full Text Available To express the negative effects of soil compaction, some researchers use critical values for soil mechanical strength that severely impair plant growth. The aim of this study was to identify this critical compaction depth, to test the functionality of a new, portable penetrometer developed from a spring dynamometer, and compare it to an electronic penetrometer traditionally used in compaction studies of agricultural soils. Three soils with distinct texture were conventionally tilled using a disk plow, and cultivated with different plant species. The critical soil resistance defined to establish critical compaction depth was equal to 1.5 MPa. The results of the new equipment were similar to the electronic penetrometer, indicating its viability as a tool for assessing the soil physical conditions for plant growth.

  2. A high sensitivity test of the Pauli Exclusion Principle for electrons

    International Nuclear Information System (INIS)

    One of the fundamental rules of nature and a pillar in the foundation of quantum theory and thus of modern physics is represented by the Pauli Exclusion Principle. We know that this principle is extremely well fulfilled due to many observations like the order of the elements and the stability of matter. Numerous experiments were performed to search for tiny violation of this rule in various systems. The VIP experiment at Gran Sasso underground laboratory is testing the validity of this principle for electrons with very high precision (order of 10-30). The layout of the present experiment, results obtained so far and new ideas to further increase the precision will be presented.

  3. Susceptibility Testing

    Science.gov (United States)

    ... page helpful? Also known as: Sensitivity Testing; Drug Resistance Testing; Culture and Sensitivity; C & S; Antimicrobial Susceptibility Formal name: Bacterial and Fungal Susceptibility Testing Related tests: Urine Culture ; ...

  4. Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

    Directory of Open Access Journals (Sweden)

    Newton Paul N

    2011-12-01

    Full Text Available Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA containing paracetamol (acetaminophen, counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

  5. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.

    Science.gov (United States)

    McCarthy, James S; Marquart, Louise; Sekuloski, Silvana; Trenholme, Katharine; Elliott, Suzanne; Griffin, Paul; Rockett, Rebecca; O'Rourke, Peter; Sloots, Theo; Angulo-Barturen, Iñigo; Ferrer, Santiago; Jiménez-Díaz, María Belén; Martínez, María-Santos; Hooft van Huijsduijnen, Rob; Duparc, Stephan; Leroy, Didier; Wells, Timothy N C; Baker, Mark; Möhrle, Jörg J

    2016-06-01

    Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ(-/-) (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.). PMID:27044554

  6. 评价螺旋体乳胶快速反应实验检测梅毒血清的特异性和敏感性%Sensitivity and specificity of Diesse syphilis fast test in testing syphilis serum

    Institute of Scientific and Technical Information of China (English)

    晋红中; 王家璧; 王晓蜂; 邵燕玲; 何志新; 刘跃华; 洪少林

    2003-01-01

    Objective: To assess sensitivity and specificity of Diesse syphilis fast test(DSFT) in routine use, and compare it with rapid plasma reagin circle card test(RPR test), Treponema pallidum particle agglutination assay(TPHA), fluorescent treponemal antibody absorption test(FTA-ABS test). Methods: DSFT, RPR, TPHA, FTA-ABS were used to detect 500 cases of syphilis and normal senam. Results :Using FTA-ABS as gold standard, the sensitivity and specificity of DSFT were 98.6% (204/207), and 93.2%(273/293) ,respectirely(X2= 1.04, P > 0.05. Using TPHA as gold standard, the sensitivity and specifity of DSFT were 100% (223/223),99.6% (273/277), respectively(x2 = 0.04, P > 0.05). Condusion: The Diesse syphilis fast test in routine use has high sensitivity and specificity in testing syphilis.

  7. The Sensitivity, Specificity and Predictive Values of Snellen Chart Compared to the Diagnostic Test in Amblyopia Screening Program in Iran

    Directory of Open Access Journals (Sweden)

    Fatemeh Rivakani

    2015-12-01

    Full Text Available Introduction Amblyopia is a leading cause of visual impairment in both childhood and adult populations. Our aim in this study was to assess the epidemiological characteristics of the amblyopia screening program in Iran. Materials and Methods A cross-sectional study was done on a randomly selected sample of 4,636 Iranian children who were referred to screening program in 2013 were participated in validity study, too. From each provinces the major city were selected. Screening and diagnostic tests were done by instructors in first stage and optometrists in second stage, respectively. Finally data were analyzed by Stata version 13. Results The sensitivity was ranged from 74% to 100% among the various provinces such that Fars and Ardabil province had maximum and minimum values, respectively. The pattern of specificity was differ and ranged 44% to 84% among the provinces; Hormozgan and Fars had maximum and minimum values, respectively. The positive predictive value was also ranged from 35% to %81 which was assigned to Khuzestan and Ardabil provinces, respectively. The range of Negative Predictive value was 61% to 100% which was belonged to Ardabil and Fars provinces. Conclusion The total sensitivity (89% and negative predictive values (93% of screening test among children aged 3-6 years is acceptable, but only 51% of children refereed to second stage are true positive and this imposes considerable cost to health system.

  8. Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

    Science.gov (United States)

    Wang, Chunying; Hou, Fei; Ma, Yicai

    2015-06-15

    A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. PMID:25562743

  9. p-Phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Andersen, Klaus Ejner; Bruze, Magnus;

    2009-01-01

    BACKGROUND: Positive patch test reactions to p-phenylenediamine (PPD) are common. PPD is used in oxidative hair dyes and is also present in dark henna temporary 'tattoos'. Cross-sensitization to other contact allergens may occur. Because subjects sensitized to PPD are at risk of clinically severe...... reactions upon hair dyeing, there is a need for 'current' prevalence data on PPD sensitization. OBJECTIVES: To compare PPD patch test results from dermatitis patients tested between 2003 and 2007 in 10 European patch test centres and to analyse the causes and determine relevance of positive PPD patch test...... reactions to PPD that were registered as being of either current or 'past' relevance was high (weighted average 53.6% and 20.3%, respectively). Consumer hair dyeing was the most prominent cause of PPD sensitization (weighted average 41.8%). Furthermore, occupational hair dye exposure (10.6%) and cross...

  10. Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Travers Dominique

    2011-01-01

    Full Text Available Abstract Background The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. Methods The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine by the standard 42-hour 3H-hypoxanthine uptake inhibition method using the Genbag CO2® system and compared to controlled incubator conditions (5% CO2 and 10% O2. Results The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O2 were significantly higher than those of Genbag® conditions (2738 cpm vs 2282 cpm, p 50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011 and higher for the quinolines: chloroquine (127 vs 94 nM, p 50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine. To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag® conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O2, 611 nM for quinine (vs 800 nM, 30 nM for mefloquine (vs 30 nM, 61 nM for monodesethylamodiaquine (vs 80 nM and 1729 nM for pyrimethamine (vs 2000 nM. Conclusions The atmospheric generators for capnophilic bacteria Genbag CO2® is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro

  11. Eclipses observed by LYRA - a sensitive tool to test the models for the solar irradiance

    CERN Document Server

    Shapiro, A I; Dominique, M; Shapiro, A V

    2012-01-01

    We analyze the light curves of the recent solar eclipses measured by the Herzberg channel (200-220 nm) of the Large Yield RAdiometer (LYRA) onboard PROBA-2. The measurements allow us to accurately retrieve the center- to-limb variations (CLV) of the solar brightness. The formation height of the radiation depends on the observing angle so the examination of the CLV provide information about a broad range of heights in the solar atmosphere. We employ the 1D NLTE radiative transfer COde for Solar Irradiance (COSI) to model the measured light curves and corresponding CLV dependencies. The modeling is used to test and constrain the existing 1D models of the solar atmosphere, e.g. the temperature structure of the photosphere and the treatment of the pseudo- continuum opacities in the Herzberg continuum range. We show that COSI can accurately reproduce not only the irradiance from the entire solar disk, but also the measured CLV. It hence can be used as a reliable tool for modeling the variability of the spectral so...

  12. Uncertainty and sensitivity analyses of the Kozloduy pump trip test by coupled RELAP5/PARCS code

    Energy Technology Data Exchange (ETDEWEB)

    Bousbia Salah, A. [Pisa Univ., Facolta di Ingegneria, DIMNP (Italy); Kliem, S.; Rohde, U. [Forschungszentrum Rossendorf (FZR) (Germany)

    2005-07-01

    The modeling of complex transients in Nuclear Power Plants (NPP) remains a challenging topic for Best Estimate three-dimensional coupled code computational tools. This technique is, nowadays, extensively used since it allows decreasing conservatism in the calculation models and performs more realistic simulating and more precise consideration of multidimensional effects under complex transients in NPPs. In the current paper a contribution to the assessment and validation of coupled code technique through the Kozloduy VVER100 pump trip test is performed. For this purpose, the coupled RELAP5/3.3-PARCS/2.6 code is used. The code results were assessed against experimental data and the comparison study shows good agreements between the calculations and the global kinetic and thermal-hydraulic aspects observed experimentally. It appears that at steady state level, the simulation errors are mainly due to the absence of ADF correction and to the model used for evaluating the Doppler feedback effect. During the transient, the discrepancies are mainly due to the combined effect of uncertain parameters related to the measurement of control rod course, and the estimation of the Doppler effect.

  13. A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

    Science.gov (United States)

    Seth, J; Kellett, H A; Caldwell, G; Sweeting, V M; Beckett, G J; Gow, S M; Toft, A D

    1984-11-17

    The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism. PMID:6437538

  14. FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance

    Directory of Open Access Journals (Sweden)

    Dondorp Arjen M

    2009-10-01

    Full Text Available Abstract Background A number of molecular tools have been developed to monitor the emergence and spread of anti-malarial drug resistance to Plasmodium falciparum. One of the major obstacles to the wider implementation of these tools is the absence of practical methods enabling high throughput analysis. Here a new Zip-code array is described, called FlexiChip, linked to a dedicated software program, which largely overcomes this problem. Methods Previously published microarray probes detecting single-nucleotide polymorphisms (SNP associated with parasite resistance to anti-malarial drugs (ResMalChip were adapted for a universal microarray FlexiChip format. To evaluate the overall sensitivity of the FlexiChip package (microarray + software, the results of FlexiChip were compared to ResMalChip microarray, using the same extension probes and with the same PCR products. In both cases, sequence results were used as gold standard to calculate sensitivity and specificity. FlexiChip results obtained with a set of field isolates were then compared to those assessed in an independent reference laboratory. Results The FlexiChip package gave results identical to the ResMalChip results in 92.7% of samples (kappa coefficient 0.8491, with a standard error 0.021 and had a sensitivity of 95.88% and a specificity of 97.68% compared to the sequencing as the reference method. Moreover the method performed well compared to the results obtained in the reference laboratories, with 99.7% of identical results (kappa coefficient 0.9923, S.E. 0.0523. Conclusion Microarrays could be employed to monitor P. falciparum drug resistance markers with greater cost effectiveness and the possibility for high throughput analysis. The FlexiChip package is a promising tool for use in poor resource settings of malaria endemic countries.

  15. Synthesis and evaluation of antimalarial activity of curcumin derivatives; Sintese e avaliacao da atividade antimalarica de compostos derivados da curcumina

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Patricia Ramos; Miguel, Fabio Balbino; Almeida, Mauro Vieira de; Couri, Mara Rubia Costa [Universidade Federal de Juiz de Fora (UFSJ), MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Oliveira, Michael Eder de; Ferreira, Vanessa Viana; Guimaraes, Daniel Silqueira Martins; Lima, Aline Brito de; Barbosa, Camila de Souza; Oliveira, Mariana Amorim de; Almeida, Mauro Vieira de; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla, E-mail: varotti@ufsj.edu.br [Universidade Federal de Sao Joao Del Rei (UFSJ), MG (Brazil). Centro de Ciencias da Saude; and others

    2014-05-15

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC{sub 50} values ranging from 1.7 to 15.2 μg mL{sup -1}), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  16. Haemoglobin interference and increased sensitivity of fluorimetric assays for quantification of low-parasitaemia Plasmodium infected erythrocytes

    Directory of Open Access Journals (Sweden)

    Puyet Antonio

    2009-12-01

    Full Text Available Abstract Background Improvements on malarial diagnostic methods are currently needed for the correct detection in low-density Plasmodium falciparum infections. Microfluorimetric DNA-based assays have been previously used for evaluation of anti-malarial drug efficacy on Plasmodium infected erythrocytes. Several factors affecting the sensitivity of these methods have been evaluated, and tested for the detection and quantification of the parasite in low parasitaemia conditions. Methods Parasitaemia was assessed by measuring SYBRGreen I® (SGI and PicoGreen® (PG fluorescence of P. falciparum Dd2 cultures on human red blood cells. Different modifications of standard methods were tested to improve the detection sensitivity. Calculation of IC50 for chloroquine was used to validate the method. Results Removal of haemoglobin from infected red-blood cells culture (IRBC increased considerably the fluorescent signal obtained from both SGI and PG. Detergents used for cell lysis also showed to have an effect on the fluorescent signal. Upon depletion of haemoglobin and detergents the fluorescence emission of SGI and PG increased, respectively, 10- and 60-fold, extending notably the dynamic range of the assay. Under these conditions, a 20-fold higher PG vs. SGI fluorescent signal was observed. The estimated limits of detection and quantification for the PG haemoglobin/detergent-depleted method were 0.2% and 0.7% parasitaemia, respectively, which allow the detection of ~10 parasites per microliter. The method was validated on whole blood-infected samples, displaying similar results as those obtained using IRBC. Removal of white-blood cells prior to the assay allowed to increase the accuracy of the measurement, by reducing the relative uncertainty at the limit of detection from 0.5 to 0.1. Conclusion The use of PG microassays on detergent-free, haemoglobin-depleted samples appears as the best choice both for the detection of Plasmodium in low-density infections

  17. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

    OpenAIRE

    Hubbard Alan E; Dorsey Grant; Gupta Vinay; Rosenthal Philip J; Greenhouse Bryan

    2010-01-01

    Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary elec...

  18. Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel)

    OpenAIRE

    Jourdan, Joëlle; Matile, Hugues; Reift, Ellen; Biehlmaier, Oliver; Dong, Yuxiang; Wang, Xiaofang; Mäser, Pascal; Vennerstrom, Jonathan L.; Wittlin, Sergio

    2015-01-01

    The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite the critical importance of artemisinin combination therapies (ACTs), the precise mode of action of peroxidic antimalarials is not fully understood. However, it has long been proposed that the peroxide bond in artemisi...

  19. Evaluation of antimalarial activity of leaves of Acokanthera schimperi and Croton macrostachyus against Plasmodium berghei in Swiss albino mice

    OpenAIRE

    Mohammed, Tigist; Erko, Berhanu; Giday, Mirutse

    2014-01-01

    Background Malaria is one of the most important tropical diseases and the greatest cause of hospitalization and death. Recurring problems of drug resistance are reinforcing the need for finding new antimalarial drugs. In this respect, natural plant products are the main sources of biologically active compounds and have potential for the development of novel antimalarial drugs. A study was conducted to evaluate extracts of the leaves of Croton macrostachyus and Acokanthera schimperi for their ...

  20. Development of a Specific Monoclonal Antibody-Based ELISA to Measure the Artemether Content of Antimalarial Drugs

    OpenAIRE

    Suqin Guo; Yongliang Cui; Lishan He; Liang Zhang; Zhen Cao; Wei Zhang; Rui Zhang; Guiyu Tan; Baomin Wang; Liwang Cui

    2013-01-01

    Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemethe...

  1. Antimalarial potential of homeopathic medicines against schizont maturation of Plasmodium berghei in short-term in vitro culture

    OpenAIRE

    Upma Bagai; Aswathy Rajan

    2012-01-01

    In vitro assessment of antimalarial drug susceptibility of Plasmodium has been a major research success, which has paved the way for the understanding of parasite and rapid screening of antimalarial drugs for their effectiveness. In the present study a preliminary screening to check the antiplasmodial activity of mother tincture (ϕ) and various potencies (6C, 30C, 200C) of homeopathic medicines Cinchona officinalis/china (Chin.), Chelidonium majus (Chel.) and Arsenicum album (Ars.) were done ...

  2. Pilot Test of a Culturally Sensitive Hypertension Management Intervention Protocol for Older Chinese Immigrants: Chinese Medicine as Longevity Modality.

    Science.gov (United States)

    Li, Wen-Wen; Gomez, Cynthia A; Tam, Jocelyn Wing-Yin

    2015-11-01

    Hypertension control in older Chinese immigrants remains a significant health issue because of their unique cultural health practices to manage their hypertension. At present, there are limited culturally sensitive health education materials regarding hypertension management tailored for the older Chinese population available for and feasible to use. Because the San Francisco Bay Area has a large population of older Chinese immigrants, development of a culturally appropriate intervention is important to help this population achieve better blood pressure control. The focus of this study was to develop and test the feasibility of a culturally sensitive hypertension management intervention protocol, Chinese Medicine as Longevity Modality. This intervention protocol is implemented as a patient education health program delivered via video format in combination with an individual consultation provided by a nurse in the initial intervention, followed by four phone calls between the initial intervention and the second follow-up visit. The results of the study showed that the proposed intervention protocol was acceptable for the target population. PMID:26571335

  3. Ecological risk assessment of organic waste amendments using the species sensitivity distribution from a soil organisms test battery

    International Nuclear Information System (INIS)

    Safe amendment rates (the predicted no-effect concentration or PNEC) of seven organic wastes were estimated from the species sensitivity distribution of a battery of soil biota tests and compared with different realistic amendment scenarios (different predicted environmental concentrations or PEC). None of the wastes was expected to exert noxious effects on soil biota if applied according either to the usual maximum amendment rates in Europe or phosphorus demands of crops (below 2 tonnes DM ha-1). However, some of the wastes might be problematic if applied according to nitrogen demands of crops (above 2 tonnes DM ha-1). Ammonium content and organic matter stability of the studied wastes are the most influential determinants of the maximum amendment rates derived in this study, but not pollutant burden. This finding indicates the need to stabilize wastes prior to their reuse in soils in order to avoid short-term impacts on soil communities. - Ecological risk assessment of organic waste amendments

  4. Patch Testing with Main Sensitizers Does Not Detect All Cases of Contact Allergy to Oxidized Lavender Oil.

    Science.gov (United States)

    Hagvall, Lina; Christensson, Johanna Bråred

    2016-06-15

    Lavender oil is an essential oil obtained from lavender (Lavendula angustifolia). The main components linalool and linalyl acetate have been shown to autoxidize in contact with oxygen in the air, forming sensitizing hydroperoxides. Patients with suspected allergic contact dermatitis were consecutively patch-tested with oxidized lavender oil 6% pet., oxidized linalyl acetate 6% pet., and oxidized linalool 6% pet. to investigate the frequency of contact allergy to oxidized lavender oil, and the pattern of concomitant reactions to oxidized linalool and oxidized linalyl acetate. Positive reactions to oxidized lavender oil were found in 2.8% of the patients. Among those, 56% reacted to oxidized linalool and/or oxidized linalyl acetate, while 52% reacted to the fragrance markers of the baseline series. Oxidized lavender oil showed among the highest frequencies of contact allergy to studied essential oils. A well-standardized preparation of oxidized lavender oil could be a useful tool for diagnosis of contact allergy to fragrances. PMID:26671837

  5. Sensitivity and alternative operating point studies on a high charge CW FEL injector test stand at CEBAF

    International Nuclear Information System (INIS)

    A high charge CW FEL injector test stand is being built at CEBAF based on a 500 kV DC laser gun, a 1500 MHz room-temperature buncher, and a high-gradient (∼10 MV/m) CEBAF cryounit containing two 1500 MHz CEBAF SRF cavities. Space-charge-dominated beam dynamics simulations show that this injector should be an excellent high-brightness electron beam source for CW UV FELs if the nominal parameters assigned to each component of the system are experimentally achieved. Extensive sensitivity and alternative operating point studies have been conducted numerically to establish tolerances on the parameters of various injector system components. The consequences of degraded injector performance, due to failure to establish and/or maintain the nominal system design parameters, on the performance of the main accelerator and the FEL itself are discussed

  6. Sensitivities of a Standard Test Method for the Determination of the pHe of Bioethanol and Suggestions for Improvement

    Directory of Open Access Journals (Sweden)

    Paul J. Brewer

    2010-11-01

    Full Text Available An assessment of the sensitivities of the critical parameters in the ASTM D6423 documentary standard method for the measurement of pHe in (bioethanol has been undertaken. Repeatability of measurements made using the same glass electrode and reproducibility between different glass electrodes have been identified as the main contributors to the uncertainty of the values produced. Strategies to reduce the uncertainty of the measurement have been identified and tested. Both increasing the time after which the pHe measurement is made following immersion in the sample, and rinsing the glass electrode with ethanol prior to immersion in the sample, have been shown to be effective in reducing the uncertainty of the numerical value produced. However, it is acknowledged that the values produced using these modified approaches may not be directly compared with those obtained using the documentary ASTM method since pHe is defined operationally by the process used to measure it.

  7. Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach.

    Science.gov (United States)

    N, Nagasundaram; C, George Priya Doss; Chakraborty, Chiranjib; V, Karthick; D, Thirumal Kumar; V, Balaji; R, Siva; Lu, Aiping; Ge, Zhang; Zhu, Hailong

    2016-01-01

    Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations. Furthermore, we performed virtual screening to identify potential compounds to inhibit the PfATP6 mutant proteins. In this study, we observed that artemisinin binding affinity with PfATP6 gets affected by L263D, L263E and L263K mutations. This in silico elucidation of artemisinin resistance enhanced the identification of novel compounds (CID: 10595058 and 10625452) which showed good binding affinity and efficacy with L263D, L263E and L263K mutant proteins in molecular docking and molecular dynamics simulations studies. Owing to the high propensity of the parasite to drug resistance the need for new antimalarial drugs will persist until the malarial parasites are eventually eradicated. The two compounds identified in this study can be tested in in vitro and in vivo experiments as possible candidates for the designing of new potential antimalarial drugs. PMID:27471101

  8. Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach

    Science.gov (United States)

    Nagasundaram, N.; George Priya Doss, C.; Chakraborty, Chiranjib; Karthick, V.; Thirumal Kumar, D.; Balaji, V.; Siva, R.; Lu, Aiping; Ge, Zhang; Zhu, Hailong

    2016-07-01

    Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations. Furthermore, we performed virtual screening to identify potential compounds to inhibit the PfATP6 mutant proteins. In this study, we observed that artemisinin binding affinity with PfATP6 gets affected by L263D, L263E and L263K mutations. This in silico elucidation of artemisinin resistance enhanced the identification of novel compounds (CID: 10595058 and 10625452) which showed good binding affinity and efficacy with L263D, L263E and L263K mutant proteins in molecular docking and molecular dynamics simulations studies. Owing to the high propensity of the parasite to drug resistance the need for new antimalarial drugs will persist until the malarial parasites are eventually eradicated. The two compounds identified in this study can be tested in in vitro and in vivo experiments as possible candidates for the designing of new potential antimalarial drugs.

  9. Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against Plasmodium falciparum: design, synthesis and biological evaluation.

    Science.gov (United States)

    Buskes, Melissa J; Harvey, Katherine L; Richards, Benjamin J; Kalhor, Robabeh; Christoff, Rebecca M; Gardhi, Chamodi K; Littler, Dene R; Cope, Elliott D; Prinz, Boris; Weiss, Greta E; O'Brien, Nathan J; Crabb, Brendan S; Deady, Leslie W; Gilson, Paul R; Abbott, Belinda M

    2016-05-18

    Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases. Parasite kinases are emerging as novel antimalarial targets as they have diverged sufficiently from their mammalian counterparts to allow selectable therapeutic action. Parasite protein kinase A (PfPKA) is highly expressed late in the cell cycle of the parasite blood stage and has been shown to phosphorylate a critical invasion protein, Apical Membrane Antigen 1. This enzyme could therefore be a valuable drug target so we have repurposed a substituted 4-cyano-3-methylisoquinoline that has been shown to inhibit rat PKA with the goal of targeting PfPKA. We synthesised a novel series of compounds and, although many potently inhibit the growth of chloroquine sensitive and resistant strains of P. falciparum, they were found to have minimal activity against PfPKA, indicating that they likely have another target important to parasite cytokinesis and invasion. PMID:27105169

  10. Quantitative structure-activity relationships of the antimalarial agent artemisinin and some of its derivatives - a DFT approach.

    Science.gov (United States)

    Rajkhowa, Sanchaita; Hussain, Iftikar; Hazarika, Kalyan K; Sarmah, Pubalee; Deka, Ramesh Chandra

    2013-09-01

    Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive Plasmodium falciparum W-2 clone. PMID:23597248

  11. Assessing the sensitivity and specificity of First Response HIV-1-2 test kit with whole blood and serum samples: a cross-sectional study

    OpenAIRE

    Boadu, Raymond; Darko, George; Nortey, Priscilla; Akweongo, Patricia; Sarfo, Bismark

    2016-01-01

    Background Human immunodeficiency virus (HIV) Rapid diagnostic Test (RDT) kits are the preferred assays for HIV testing in many countries. Prevention of Mother-to-Child Transmission, Know Your Status Campaigns, Blood-Safety, Voluntary Counseling and Testing are major strategies adapted to control transmission of the virus and the pivot of these interventions is either screening or diagnosing individuals through testing. There are reports of inconsistent sensitivity and specificity with whole ...

  12. Effect of molecular weight and testing rate on adhesion property of pressure-sensitive adhesives prepared from epoxidized natural rubber

    International Nuclear Information System (INIS)

    Research highlights: → Elucidation of adhesion property of epoxidized natural rubber (ENR 25). → Correlation of peel and shear strength with molecular weight and rate of testing. → Confirmation of miscibility of tackifier and ENR 25 by DSC and FTIR study. → Applicability of Fox equation in ENR 25/coumarone-indene resin system. -- Abstract: The dependence of peel strength and shear strength of epoxidized natural rubber (ENR 25)-based pressure-sensitive adhesive on molecular weight and rate of testing was investigated using coumarone-indene as the tackifying resin. Toluene and polyethylene terephthalate (PET) were used as the solvent and substrate respectively throughout the study. A SHEEN hand coater was used to coat the adhesive on the substrate at a coating thickness of 120 μm. All the adhesion properties were determined by a Llyod Adhesion Tester operating at different rates of testing. Result shows that peel strength and shear strength increases up to an optimum molecular weight of 6.5 x 104 of ENR 25. For peel strength, the observation is attributed to the combined effects of wettability and mechanical strength of rubber at the optimum molecular weight, whereas for the shear strength, it is ascribed to the increasing amount of adhesive present in the coating layer which enhances the shear resistance of the adhesive. Peel strength and shear strength also increases with increase in rate of testing, an observation which is associated to the viscoeslastic response of the adhesive. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) study confirms the miscibility of tackifier and the ENR 25.

  13. Evaluation of a Novel Rapid Test System for the Detection of Allergic Sensitization to Timothy Grass Pollen against Established Laboratory Methods and Skin Prick Test

    Directory of Open Access Journals (Sweden)

    R. Lucassen

    2010-01-01

    Full Text Available Type I hypersensitivity is driven by allergen specific immunoglobulin E (sIgE and thus sIgE represents a marker for modern allergy diagnosis. Recently, a rapid assay for the detection of sIgE, termed as (Allergy Lateral Flow Assay ALFA, has been developed. The objective of our study is the evaluation of a scanner-based system for the semiquantitative interpretation of ALFA results. Agreement to Skin Prick Test (SPT, Allergopharma, ALLERG-O-LIQ System (Dr. Fooke, and ImmunoCAP (Phadia was investigated using 50 sera tested for specific IgE to timothy grass pollen (g6. 35/50 sera were positive by SPT, ALLERG-O-LIQ, and ImmunoCAP. Excellent agreement was observed between ALFA results and SPT, ImmunoCAP, and ALLERG-O-LIQ. Area under the curve (AUC values were found at 1.0, and 100% sensitivity and specificity was found versus all other methods. Visual- and scanner-based interpretation of the ALFA results revealed excellent agreement.

  14. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    Science.gov (United States)

    Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

    2015-01-01

    Summary There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. We describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the parasite, with good pharmacokinetic properties, and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery. PMID:26085270

  15. Saleability of anti-malarials in private drug shops in Muheza, Tanzania

    DEFF Research Database (Denmark)

    Ringsted, Frank M; Massawe, Isolide S; Lemnge, Martha M;

    2011-01-01

    women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a...... baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods: All drug shops selling...... resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp strategy. Further studies are recommended to find out barriers for ACT utilization and preference for self-medication and to train private drug...

  16. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    Science.gov (United States)

    Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W.; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth A.; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul A.; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

    2015-06-01

    There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

  17. Enhanced Low Dose Rate Sensitivity (ELDRS) tests on advanced SiGe bipolar transistors for very high total dose applications

    International Nuclear Information System (INIS)

    A new comprehensive method for assessing Enhanced Low Dose Rate Sensitivity (ELDRS) in bipolar transistors to be used for very high total doses is applied to an advanced SiGe HBT technology for its use in the ATLAS Upgrade at CERN. Conventional ELDRS assessment methods are combined with switched experiments (high/low dose rate), providing a way to verify the presence of ELDRS at very high doses in reasonable irradiation time. Additionally, an anomalous damage recovery has been found in transistors with saturated damage after further low dose rate irradiations. -- Highlights: • It has been demonstrated that the bipolar technology under study does not show ELDRS in the whole range of total doses studied. • The previous radiation hardness tests of a SiGe HBT technology have been validated. • A new ELDRS test strategy is presented for ELDRS in very high total dose applications. • An anomalous damage recovery has been observed in switched dose rate experiments in the saturation region

  18. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    Science.gov (United States)

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-05-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific. PMID:25991720

  19. Hallazgos complementarios sobre la actividad antimalarica del azul de metileno = Complementary findings on the antimalarial activity and toxicity of methylene blue

    OpenAIRE

    G. Garavito; Bertani, S; Deharo, Eric

    2008-01-01

    Methylene blue was reported as the first synthetic antimalarial by Ehrlich in 1881. It is currently no longer used for that purpose but it should be reconsidered since new economic alternatives are urgently needed in the arsenal of antimalarial drugs. The antimalarial activity of methylene blue is investigated here in vivo against rodent malaria parasites. 15 mg/kg daily dose of methylene blue inhibits 50% of the erythrocytic parasite growth of Plasmodium berghei and R yoelii nigeriensis, whi...

  20. Estimation of sensitivity, specificity and predictive values of two serologic tests for the detection of antibodies against Actinobacillus pleuropneumoniae serotype 2 in the absence of a reference test (gold standard)

    DEFF Research Database (Denmark)

    Enøe, Claes; Andersen, Søren; Sørensen, Vibeke; Willeberg, Preben

    independence was assumed to models allowing for conditional dependence, given the true disease status. No strong evidence of conditional dependence in either test sensitivity or specificity was found. Assuming independence, maximum-likelihood estimates and 95% confidence intervals of the sensitivity and...