WorldWideScience

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.

    Directory of Open Access Journals (Sweden)

    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. Antimalarial peroxides

    Directory of Open Access Journals (Sweden)

    DEJAN M. OPSENICA

    2009-11-01

    Full Text Available The problem of endemic malaria continues unabated globally. Malaria affects 40 % of the global population, causing an estimated annual mortality of 1.5–2.7 million people. The World Health Organization (WHO estimates that 90 % of these deaths occur in sub-Saharan Africa among infants under the age of five. While a vaccine against malaria continues to be elusive, chemotherapy remains the most viable alternative towards treatment of the disease. During last years, the situation has become urgent in many ways, but mainly because of the development of chloroquine-resistant (CQR strains of Plasmodium falciparum (Pf. The discovery that artemisinin (ART, 1, an active principle of Artemisia annua L., expresses a significant antimalarial activity, especially against CQR strains, opened new approaches for combating malaria. Since the early 1980s, hundreds of semisynthetic and synthetic peroxides have been developed and tested for their antimalarial activity, the results of which were extensively reviewed. In addition, in therapeutic practice, there is no reported case of drug resistance to these antimalarial peroxides. This review summarizes recent achievements in the area of peroxide drug development for malaria chemotherapy.

  4. In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity.

    Science.gov (United States)

    Lucchi, Naomi W; Komino, Franklin; Okoth, Sheila Akinyi; Goldman, Ira; Onyona, Philip; Wiegand, Ryan E; Juma, Elizabeth; Shi, Ya Ping; Barnwell, John W; Udhayakumar, Venkatachalam; Kariuki, Simon

    2015-12-01

    Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.

  5. Plants as Sources of Antimalarial Drugs Part. 1. In vitro Test Method for the Evaluation of Crude Extracts from Plants.

    Science.gov (United States)

    O'neill, M J; Bray, D H; Boardman, P; Phillipson, J D; Warhurst, D C

    1985-10-01

    An IN VITRO antimalarial test, utilising the inhibition of uptake of [G- (3)H]-hypoxanthine into PLASMODIUM FALCIPARUM cultured in human blood, has been used to assess the activity of crude extracts of ARTEMISIA ANNUA and A. VULGARIS (Compositae) and of BRUCEA JAVANICA, AILANTHUS ALTISSIMA, and SIMABA CEDRON (Simaroubaceae).

  6. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part IV. Is a new haem polymerisation inhibition test pertinent for the detection of antimalarial natural products?

    Science.gov (United States)

    Baelmans, R; Deharo, E; Bourdy, G; Muñoz, V; Quenevo, C; Sauvain, M; Ginsburg, H

    2000-11-01

    The search for new antimalarial agents in plant crude extracts using traditional screening tests is time-consuming and expensive. New in vitro alternative techniques, based on specific metabolic or enzymatic process, have recently been developed to circumvent testing of antimalarial activity in parasite culture. The haem polymerisation inhibition test (HPIA) was proposed as a possible routine in vitro assay for the detection of antimalarial activity in natural products. A total of 178 plant extracts from the Pharmacopeia of the Bolivian ethnia Tacana, were screened for their ability to inhibit the polymerisation of haematin. Five extracts from Aloysia virgata (Ruíz & Pavón) A.L. Jussieu (Verbenaceae), Bixa orellana L. (Bixaceae), Caesalpinia pluviosa D.C. (Caesalpiniaceae), Mascagnia stannea (Griseb) Nied. (Malpighiaceae) and Trichilia pleenea (Adr. Jussieu) (Meliaceae) demonstrated more than 70% inhibition of haematin polymerisation at 2.5 mg/ml. The extracts were also tested for antimalarial activity in culture against F32 strain (chloroquine-sensitive) and D2 strain (chloroquine-resistant) of Plasmodium falciparum and in vivo against P. berghei. The extract from Caesalpinia pluviosa was the only one that showed activity in HPIA and in the classical test in culture. The accuracy and pertinence of HPIA, applied to natural products is discussed. PMID:11025165

  7. Antimalarial activity of cedronin.

    Science.gov (United States)

    Moretti, C; Deharo, E; Sauvain, M; Jardel, C; David, P T; Gasquet, M

    1994-06-01

    Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. 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...

  11. 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.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer

    Science.gov (United States)

    Cufí, Sílvia; Vazquez-Martin, Alejandro; Oliveras-Ferraros, Cristina; Corominas-Faja, Bruna; Cuyàs, Elisabet; López-Bonet, Eugeni; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A.

    2013-01-01

    Autophagy may control the de novo refractoriness of HER2 gene-amplified breast carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells originally obtained from a patient who rapidly progressed on trastuzumab ab initio display increased cellular levels of the LC3-II protein—a finding that correlates with increased numbers of autophagosomes—and decreased levels of the autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy. Trastuzumab-refractory cells are in a state of “autophagy addiction” because genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic drug chloroquine impedes autophagic resolution of the accumulation of autophagolysosomes formed in the presence of trastuzumab, cells commit to die by apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine radically suppresses tumor growth by > 90% in a tumor xenograft completely refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may therefore improve outcomes among women with autophagy-addicted HER2-positive breast cancer. PMID:23965851

  14. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    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.

  15. An improved and highly sensitive microfluorimetric method for assessing susceptibility of Plasmodium falciparum to antimalarial drugs in vitro

    Directory of Open Access Journals (Sweden)

    Ranford-Cartwright Lisa C

    2006-10-01

    Full Text Available Abstract Background The standard in vitro protocol currently in use for drug testing against Plasmodium falciparum, based on the incorporation of the purine [3H]-hypoxanthine, has two serious drawbacks. Firstly it is unsuitable for the testing of drugs that directly or indirectly impact on purine salvage or metabolism. Secondly, it relies on the use of expensive radiolabelled material, with added issues concerning detection, storage and waste disposal that make it unsuitable for use in many disease-endemic areas. Recently, the use of fluorochromes has been suggested as an alternative, but quenching of the fluorescence signal by the haemoglobin present in cultures of Plasmodium falciparum-infected erythrocytes severely limits the usefulness of this approach. Methods In order to resolve this problem, a new PicoGreen®-based procedure has been developed which incorporates additional steps to remove the interfering haemoglobin. The 50% inhibitory concentration (IC50 values of chloroquine and pyrimethamine against P. falciparum laboratory lines 3D7 and K1 were determined using the new protocol. Results The IC50 values of chloroquine and pyrimethamine against P. falciparum laboratory lines 3D7 and K1 determined with the new fluorescence-based protocol were statistically identical to those obtained using the traditional 3H-hypoxanthine incorporation method, and consistent with literature values. Conclusion The new method proved to be accurate, reproducible and sensitive, and has the advantage of being non-radioactive. The improved PicoGreen® method has the potential to replace traditional in vitro drug resistance assay techniques.

  16. 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...

  17. In vitro sensitivity of chloroquine sensitive and resistant Plasmodium falciparum to artemisinin antimalarials%恶性疟原虫氯喹敏感株与抗性株对青蒿素类药物体外敏感性的研究

    Institute of Scientific and Technical Information of China (English)

    黄芳; 冯晓平; 周水森; 汤林华

    2008-01-01

    目的 测定恶性疟原虫氯喹敏感株与抗性株对青蒿素类药物的体外敏感性. 方法 运用体外微量法与酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定青蒿琥酯、蒿甲醚及双氢青蒿素等3种青蒿素类抗疟药物对体外培养的恶性疟原虫氯喹敏感株与氯喹抗性株的体外敏感性,并比较两种方法测定的IC50值. 结果 体外微量法测定的3种药物对恶性疟原虫氯喹敏感株的IC50值依次为3.12 nmol/L、4.30 nmol/L、2.18 nmol/L,对恶性疟原虫氯喹抗性株的IC50值依次为4.31nmol/L、3.90 nmol/L、3.17 nmol/L;同时,将体外微量法与ELISA法所获的结果进行相关性分析,两种方法结果基本一致(r2=0.93,P<0.001). 结论 恶性疟原虫氯喹抗性株对青蒿素类药物无明显的交叉抗性;ELISA法可用于恶性疟原虫对抗疟药物的体外敏感性检测.%Objective To test the sensitivity of chloroquine sensitive and resistant Plasmodium falciparum to artemisinin anfimalarials. Method The responses of chloroquine sensitive and resistant P.falciparum to artemisinin antimalarials including artesunate,artemether and dihydroartemisinin were determined with Rieckmann s in vitro micro-technique and enzyme-linked immunosorbent assay(ELISA).The values of 50%inhibition of parasitemia(IC50)were compared with above two methods. Results The IC50 of artemisinin antimalarials in chloroquine sensitive P.falciparum were 3.12 nmoL/L,4.30 nmol/L,2.18 nmol/L respectively,while that in chloroquine resistant P. falciparum were 4.31nmol/L,3.90 nmol/L,3.17 nmol/L.The results obtained with both techniques were similar or identical by correlation analysis(r2=0.93,P<0.001).Conclusions There were no apparent cross-resistance of chloroquine resistant P.falciparum to artemisinin antimalarials.The ELISA test would be suitable for testing antimalarial drugs sensitivitv in vitro.

  18. On peroxide antimalarials

    Directory of Open Access Journals (Sweden)

    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.

  19. Skin prick test results to artesunate in children sensitized to Artemisia vulgaris L.

    Science.gov (United States)

    Mori, F; Pantano, S; Rossi, M E; Montagnani, C; Chiappini, E; Novembre, E; Galli, L; de Martino, M

    2015-09-01

    Artemisia vulgaris L and Artemisia annua L (Chinese: qinghao) are similar plants of the Asterbaceae family. Artesunate, a semi-synthetic derivate of artemisin which is the active principle extract of the plant qinghao, has antimalarial properties. Some cases of severe allergic reactions to artesunate have been described. The purpose of this study was to evaluate the association between positive skin tests to Artemisia vulgaris L allergen and a preparation of injectable artesunate. A total of 531 children were skin prick tested with inhalants (including Artemisia vulgaris L), foods, and artesunate. Among the 59 patients positive to Artemisia vulgaris L only one child was also positive to artesunate. No child was positive to artesunate in those negative to Artemisia vulgaris L. We conclude that Artemisia vulgaris L sensitization is not associated with sensitization to artesunate; consequently, skin test to artesunate should not be carried out before using the drug considering the rare allergic reactions. PMID:26157064

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Antimalarial natural products: a review

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. Component resolved testing for allergic sensitization

    DEFF Research Database (Denmark)

    Skamstrup Hansen, Kirsten; Poulsen, Lars K

    2010-01-01

    Component resolved diagnostics introduces new possibilities regarding diagnosis of allergic diseases and individualized, allergen-specific treatment. Furthermore, refinement of IgE-based testing may help elucidate the correlation or lack of correlation between allergenic sensitization and allergic...

  5. The quality of antimalarials available in Yemen

    Directory of Open Access Journals (Sweden)

    Atta Hoda

    2005-06-01

    Full Text Available Abstract Background Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. Methods Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only in comparison to standard specifications for these products in the relevant pharmacopoeia. Results The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. Conclusion There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Viira, Birgit; Gendron, Thibault; Lanfranchi, Don Antoine; Cojean, Sandrine; Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre; Maes, Louis; Maran, Uko; Loiseau, Philippe M; Davioud-Charvet, Elisabeth

    2016-06-29

    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.

  9. 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...

  10. Component resolved testing for allergic sensitization

    DEFF Research Database (Denmark)

    Skamstrup Hansen, Kirsten; Poulsen, Lars K

    2010-01-01

    Component resolved diagnostics introduces new possibilities regarding diagnosis of allergic diseases and individualized, allergen-specific treatment. Furthermore, refinement of IgE-based testing may help elucidate the correlation or lack of correlation between allergenic sensitization and allergic...... disease. Novel tools to predict severe outcomes and to plan for allergen-specific treatment are necessary, and because only a small amount of blood is needed to test for a multitude of allergens and allergenic components, component resolved diagnostics is promising. A drawback is the risk of overdiagnosis...... and misinterpretation of the complex results of such tests. Also, the practical use and selection of allergenic components need to be evaluated in large studies including well-characterized patients and healthy, sensitized controls and with representation of different geographical regions....

  11. 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

    purchase price, causing free-riding and sub-optimal private procurement, such products may be subsidized in developing countries through means-testing. Owing to associated spillover effects, cost-benefit analysis of such subsidies requires modelling behavioral responses of both the subsidized household...... and 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...... resulting from a specific targeting rule, depending on the resulting aggregate incidence of subsidy. Applying our method to the Kenyan data, we find that (i) individual ITN use rises with neighborhood subsidy-rates, (ii) under means-testing, predicted ITN use is a convex increasing function of the subsidy...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  14. 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...

  15. 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.

  16. Echinodermata in ecotoxicological tests: maintenance and sensitivity

    Directory of Open Access Journals (Sweden)

    Jocássio Batista Soares

    2016-03-01

    Full Text Available Abstract This work investigates the sensitivity of four species of Echinodermata (Lytechinus variegatus, Echinometra lucunter, Arbacia lixula and Encope emarginata, evaluating the effect of five reference toxicants (Cd, Pb, Cr, Cu and SDS on embryo-larval development, following the official protocols. It also evaluates techniques for the maintenance of L. variegatus in the laboratory, changes in its sensitivity, and the effects of chemical agents that induce the release of gametes, on the survival rates of the organisms. In terms of the maintenance of L. variegatus in the laboratory, the diet with vegetable content appears to be more favorable for maintenance and maturation in cultivation tanks. Chemical inducers such as KCl and the Anesthetic (lidocaine and epinephrine resulted in high adult mortality rates, discouraging its re-induction. The tests performed with different species of sea urchin and sand dollar, using different reference toxicants, showed no variations in sensitivity to the more toxic chemicals, indicating that different species can be used for evaluation and environmental impact assessment.

  17. 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.

  18. 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

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

    OpenAIRE

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

    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...

  20. Retrospective evaluation of the consequence of alleged patch test sensitization

    DEFF Research Database (Denmark)

    Jensen, Charlotte D; Paulsen, Evy; Andersen, Klaus E

    2006-01-01

    consequences in cases of possible patch test sensitization. Among 7619 consecutively tested eczema patients in a 14-year period 26 (0.3%) were identified in the database as having had a late patch test reaction, which may be an indication of patch test sensitization. 9 of these cases were not suitable....... For the remaining 11 patients we could not rule out that they were patch test sensitized, and they were investigated further. 1 was diseased and 10 were interviewed regarding the possible consequences of the alleged patch test sensitization. 9 had not experienced any dermatitis problems, and 1 could not exclude...

  1. 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...

  2. 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.

  3. 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

  4. 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

  5. Highly sensitive silicon microreactor for catalyst testing

    DEFF Research Database (Denmark)

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

    2009-01-01

    by directing the entire gas flow through the catalyst bed to a mass spectrometer, thus ensuring that nearly all reaction products are present in the analyzed gas flow. Although the device can be employed for testing a wide range of catalysts, the primary aim of the design is to allow characterization of model...... 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......, it is found that platinum catalysts with areas as small as 15 mu m(2) are conveniently characterized with the device. (C) 2009 American Institute of Physics. [doi:10.1063/1.3270191]...

  6. 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...

  7. 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.

  8. 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…

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis.

    Science.gov (United States)

    Santos, Cleydson Breno Rodrigues dos; Lobato, Cleison Carvalho; Braga, Francinaldo Sarges; Costa, Josivan da Silva; Favacho, Hugo Alexandre Silva; Carvalho, Jose Carlos Tavares; Macedo, Williams Jorge da Cruz; Brasil, Davi Do Socorro Barros; Silva, Carlos Henrique Tomich de Paula da; Silva Hage-Melim, Lorane Izabel da

    2015-01-01

    Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays. PMID:26017698

  16. Sensitivity and accuracy of whole effluent toxicity (WET) tests

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, G. [Environmental Protection Agency, Newport, OR (United States); Lussier, S. [Environmental Protection Agency, Narragansett, RI (United States); Norberg-King, T. [Environmental Protection Agency, Duluth, MN (United States); Poucher, S.; Thursby, G. [SAIC, Narragansett, RI (United States)

    1995-12-31

    Direct measurement of effluent toxicity is a critical tool in controlling ambient toxicity. Lack of water quality criteria for many commonly discharged chemicals and complicated toxicological interactions in complex effluents are common. Complex effluent toxicity tests should provide limits as protective as National Criteria for single chemicals. One way to evaluate WET test sensitivity and accuracy is to compare WET test results with single chemicals to the National Criteria for these chemicals. A study of eight criteria chemicals (ammonia, analine, cadmium, carbaryl, copper, lead, methyl parathion, and zinc), two freshwater WET tests (Pimephales and Ceriodaphnia), and four marine WET tests (Arbacia, Champia, Menidia, and Mysidopsis) was conducted to provide this comparison. The most sensitive of the freshwater and marine WET tests with each chemical were generally less protective than the National Final Chronic Value (FCV) concentration by factors ranging from 1.09 to 44. Less-sensitive WET tests with each chemical represented significant underestimation of chronic toxicity by factors often in the range of 100--10,000. In two instances WET test results (copper and Champia, zinc and Ceriodaphnia) were below FCV by factors of 1.85 and 3.4, respectively. It is recognized that Champia is extremely sensitive to copper and that Daphnids may not be protected by the current National zinc criterion, thus these results are not surprising. Adequate accuracy for WET tests usually requires that the most sensitive WET-test species by utilized. Although the bias of WET tests to underestimate chronic toxicity is relatively small, it should be considered in the selection of test endpoints and application of WET data.

  17. Method of Testing the Flyer Sensitivity of Explosives

    Institute of Scientific and Technical Information of China (English)

    王桂吉; 赵剑衡

    2004-01-01

    By means of Mylar flyer shock explosives driven by electric gun, the method of testing the flyer initiation sensitivity of explosives is studied, and some experiments are done. The experimental results show that the test method established is correct, which is very important and instructive to study and evaluate the safety and reliability of explosives. For the moment, the test should be researched and discussed further.

  18. The sensitivity of patch test in patients with psoriasis

    Directory of Open Access Journals (Sweden)

    Yavuz Yeşilova

    2010-09-01

    Full Text Available Objectives: Allergic diseases play an important role in the natural course of psoriasis. Atopic sensitization and con-tact dermatitis are common in patients with psoriasis. Since the symptoms are prolonged in patients who are resistant to therapy and exposure to itchy and external factors are common among these patients, the effects of contact aller-gens on triggering psoriasis are investigated. Contact allergens have an important role in activation and remission of psoriasis. We aimed to investigate contact sensitization rates in patients with psoriasis in the study.Material and Methods: Contact sensitization was investigated with the application of European standard series in twenty patients with psoriasis, twenty patients with contact dermatitis, and twenty healthy persons. Results: Among the whole study cases, positivity rate of patch test against one allergen at least was 25%. rate of patch test was 25% in patients with psoriasis, 35% in patients with contact dermatitis, and 15% in healthy persons. There were no significant differences between the groups according to sensitization to one or more allergens (p>0.05. There were no significant difference in clinical subgroup of psoriatic patients according to contact sensitiza-tion (p>0.05. The allergens in patients with psoriasis on patch test were as the followings: phenyldiamine, potassium dichromat, nickel, and cobalt.Conclusion: We think that the patch test has a major role in the diagnosis and elimination of allergens in patients with the chronic and resistant diseases and palmoplantar and flexural psoriasis.

  19. Present development concerning antimalarial activity of phospholipid metabolism inhibitors with special reference to in vivo activity

    Directory of Open Access Journals (Sweden)

    Marie L. Ancelin

    1994-01-01

    Full Text Available The systematic screening of more than 250 molecules against Plasmodium falciparum in vitro has previously shown that interfering with phospholipid metabolism is lethal to the malaria parasite. These compounds act by impairing choline transport in infected erythrocytes, resulting in phosphatidylcholine de novo biosynthesis inhibition. A thorough study was carried out with the leader compound G25, whose in vitro IC50 is 0.6 nM. It was very specific to mature parasites (trophozoïtes as determined in vitro with P. falciparum and in vivo with P. chabaudi -infected mice. This specificity corresponds to the most intense phase of phospholipid biosynthesis activity during the parasite cycle, thus corroborating the mechanism of action. The in vivo antimalarial activity (ED50 against P. chabaudi was 0.03 mg/kg, and a similar sensitivity was obtained with P. vinckei petteri, when the drug was intraperitoneally administered in a 4 day suppressive test. In contrast, P. berghei was revealed as less sensitive (3- to 20-fold, depending on the P. berghei-strain. This difference in activity could result either from the degree of synchronism of every strain, their invasion preference for mature or immature red blood cells or from an intrinsically lower sensitivity of the P. berghei strain to G25. Irrespective of the mode of administration, G25 had the same therapeutic index (lethal dose 50 (LD50/ED50 but the dose to obtain antimalarial activity after oral treatment was 100-fold higher than after intraperitoneal (or subcutaneous administration. This must be related to the low intestinal absorption of these kind of compounds. G25 succeeded to completely inhibiting parasitemia as high as 11.2% without any decrease in its therapeutic index when administered subcutaneously twice a day for at least 8 consecutive days to P. chabaudi -infected-rodent model. Transition to human preclinical investigations now requires a synthesis of molecules which would permit oral

  20. 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...

  1. LLNL Small-Scale Friction sensitivity (BAM) Test

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, L.R.; Foltz, M.F.

    1996-06-01

    Small-scale safety testing of explosives, propellants and other energetic materials, is done to determine their sensitivity to various stimuli including friction, static spark, and impact. Testing is done to discover potential handling problems for either newly synthesized materials of unknown behavior, or materials that have been stored for long periods of time. This report describes the existing {open_quotes}BAM{close_quotes} Small-Scale Friction Test, and the methods used to determine the friction sensitivity pertinent to handling energetic materials. The accumulated data for the materials tested is not listed here - that information is in a database. Included is, however, a short list of (1) materials that had an unusual response, and (2), a few {open_quotes}standard{close_quotes} materials representing the range of typical responses usually seen.

  2. 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.

  3. In vitro susceptibility of Plasmodium vivax to antimalarials in Colombia.

    Science.gov (United States)

    Fernández, Diana; Segura, César; Arboleda, Margarita; Garavito, Giovanny; Blair, Silvia; Pabón, Adriana

    2014-11-01

    The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC50s for chloroquine and artesunate were significantly different in the two aforementioned groups (P Colombia, P. vivax continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing in vitro susceptibilities of P. vivax isolates to antimalarials in Colombia.

  4. 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 ...

  5. On the use of sensitivity tests in seismic tomography

    NARCIS (Netherlands)

    Rawlinson, N.; Spakman, W.

    2016-01-01

    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 checkerboar

  6. Herd sensitivity in relation to test-sensitivity in Swine Vesicular Disease serological tests

    NARCIS (Netherlands)

    Dekker, A.

    2005-01-01

    After the swine vesicular disease (SVD) outbreaks in 1992 in the Netherlands a national monitoring programme was initiated, testing 12 samples from every pig farm three times per year. In this monitoring a slightly higher cut-off was used than the cut-off agreed on within the European community. The

  7. 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 vitro......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...... tests, and analyses of molecular markers. Data obtained with the therapeutic efficacy test conducted according to the standard protocol of the World Health Organization are most useful for updating national treatment policies, while the in vitro test and molecular markers can provide important...

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Direct Sensitivity Test of the MB/BacT System

    Directory of Open Access Journals (Sweden)

    Barreto Angela Maria Werneck

    2002-01-01

    Full Text Available In order to evaluate the direct-method test of sensitivity to drugs used in the principal tuberculosis treatment regimes, in the Organon Teknika MB/BacT system, we tested 50 sputum samples positive to microscopy taken from patients with pulmonary tuberculosis and with clinical indications for an antibiogram, admitted sequentially for examination during the routine of the reference laboratory. The material was treated v/v with 23% trisodium phosphate solution, incubated for 24 h at 35°C, and neutralized v/v with 20% monosodium phosphate solution. The material was then centrifuged and the sediment inoculated into flasks containing Rifampin - 2 µg/ml, Isoniazid - 0.2 µg/ml, Pyrazinamide - 100 µg/ml, Ethambutol - 2.5 µg/ml, Ethionamide - 1.25 µg/ml, and Streptomycin - 2 µg/ml. The tests were evaluated using the indirect method in the BACTEC 460 TB (Becton Dickinson system as the gold standard. The results showed that the Rifampin test performed best, i.e., 100% sensitivity at 95% Confidence Interval (82.2-100 and 100% specificity at 95% Confidence Interval (84.5-100, followed by Isoniazid and Pyrazinamide. In this experiment, 92% of the materials showed a final reading in 30 days; this period represents the time for primary isolation as well as the results of the sensitivity profile, and is within Centers for Disease Control and Prevention recommendations regarding time for performance of the antibiogram. The inoculated flasks showed no contamination during the experiment. The MB/BacT is shown to be a reliable, rapid, fully automated nonradiometric system for the tuberculosis antibiogram.

  17. Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase.

    Science.gov (United States)

    Sonoiki, Ebere; Palencia, Andres; Guo, Denghui; Ahyong, Vida; Dong, Chen; Li, Xianfeng; Hernandez, Vincent S; Zhang, Yong-Kang; Choi, Wai; Gut, Jiri; Legac, Jennifer; Cooper, Roland; Alley, M R K; Freund, Yvonne R; DeRisi, Joseph; Cusack, Stephen; Rosenthal, Philip J

    2016-08-01

    There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum Two 3-aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [(14)C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS.

  18. Screening for antimalarial and acetylcholinesterase inhibitory activities of some Iranian seaweeds.

    Science.gov (United States)

    Ghannadi, A; Plubrukarn, A; Zandi, K; Sartavi, K; Yegdaneh, A

    2013-04-01

    Alcoholic extracts of 8 different types of seaweeds from Iran's Persian Gulf were tested for their antimalarial and acetylcholinesterase enzyme (AChE) inhibitory activities for the first time. A modified Ellman and Ingkaninan method was used for measuring AChE inhibitory activity in which galanthamine was used as the reference. The antimalarial assay was performed using microculture radioisotope technique. Mefloquine and dihydroartemisinin were uased as the standards. The extract of Sargassum boveanum (Sargasseae family) showed the highest AChE inhibitory activity (IC50 equals to 1 mg ml(-1)) while Cystoseira indica (Cystoseiraceae family) exhibited the least activity (IC50 of 11 mg ml(-1)). The species from Rhodophyta (Gracilaria corticata and Gracilaria salicornia) also showed moderate activities (IC509.5, 8.7 mg ml(-1), respectively). All extracts were inactive in antimalarial assay. PMID:24019820

  19. Sensitivity of The Dynamic Visual Acuity Test To Sensorimotor Change

    Science.gov (United States)

    Cohen, Helen; Bloomberg, Jacob; Elizalde, Elizabeth; Fregia, Melody

    1999-01-01

    Post-flight astronauts, acutely post-vestibular nerve section patients, and patients with severe chronic bilateral vestibular deficits have oscillopsia caused by reduced vestibulocular reflex gains and decreased postural stability. Therefore, as previous work has shown, a test of dynamic visual acuity (DVA), in which the subject must read numbers from a computer screen while standing still or walking in place provides a composite measure of sensorimotor integration. This measure may be useful for determining the level of recovery, post-flight, post-operatively, or after vestibular rehabilitation. To determine the sensitivity of DVA to change in impaired populations we have tested patients with acoustic neuromas before and during the first post-operative week after resection of the tumors, and with bilaterally labyrinthine deficient subjects before and after six weeks of balance rehabilitation therapy.

  20. 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

  1. A new in vivo screening paradigm to accelerate antimalarial drug discovery.

    Directory of Open Access Journals (Sweden)

    María Belén Jiménez-Díaz

    Full Text Available The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR, which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0 of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1 or induce parasite clearance (PRR >1 with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a

  2. In vitro evaluation of marketed antimalarial chloroquine phosphate tablets

    Directory of Open Access Journals (Sweden)

    Amit K. Patel, Bhupendra G. Prajapati, Rubina S. Moria & Chhaganbhai N. Patel

    2005-12-01

    Full Text Available Background & objectives: The aim of the present study is to investigate the physicochemicalequivalence of seven brands of tablets containing chloroquine phosphate, an antimalarial purchasedfrom different retail pharmacy outlets.Methods: The quality and physicochemical equivalence of seven different brands of chloroquinephosphate tablets were assessed. The assessment included the evaluation of uniformity of weight,friability, crushing strength, disintegration and dissolution tests as well as chemical assay of thetablets.Results: All the seven brands of the tablets passed the British Pharmacopoeia (BP standards foruniformity of weight, disintegration and crushing strength. One of seven brands failed the friabilitytest. One of the brands did not comply with the standard assay of content of active ingredients.Dissolution test passes the pharmacopoeial standards for chloroquine phosphate tablets. There wereno significant differences in the amounts of chloroquine phosphate released from the different brands.Interpretation & conclusion: Out of the seven brands of anti-malarial chloroquine phosphate tabletsonly one brand fails to meet BP quality specifications which shows constant market monitoring ofnew products to ascertain their equivalency to pharmacopoeial standards.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. The role of antimalarial treatment in the elimination of malaria.

    Science.gov (United States)

    Gosling, R D; Okell, L; Mosha, J; Chandramohan, D

    2011-11-01

    With declining transmission of malaria in several regions of the world and renewed interest in the elimination of malaria, strategies for malaria control using antimalarial drugs are being revisited. Drug-based strategies to reduce transmission of malaria need to target the asymptomatic carriers of infection. Drugs that are effective against gametocytes are few in number, but it may be possible to reduce gametocyte production by killing the asexual stages, for which more drugs are available. Drugs for use in large-scale programmes must be safe and tolerable. Strategies include improving access to treatment for malaria with an efficacious drug, intermittent-treatment programmes, and mass drug administration, with and without screening for malaria. Recent proposals have targeted high-risk groups for interventions. None of the strategies has been rigorously tested with appropriate control groups for comparison. Because of the lack of field evidence, modelling has been used. Models have shown, first, that for long-lasting effects, drug administration programmes should be linked with vector control, and second, that if elimination is the aim, programmes are likely to be more successful when applied to smaller populations of a few thousand or less. In order to sustain the gains following the scaling up of vector control and use of artemisinin combination therapies (ACTs), strategies that use antimalarials effectively need to be devised and evidence generated for the most cost-efficient way forward.

  10. 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

  11. [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

  12. 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

  13. 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 ...

  14. 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...

  15. Antimalarial plants of northeast India: An overview

    Directory of Open Access Journals (Sweden)

    Rama Shankar

    2012-01-01

    Full Text Available The need for an alternative drug for malaria initiated intensive efforts for developing new antimalarials from indigenous plants. The information from different tribal communities of northeast India along with research papers, including books, journals and documents of different universities and institutes of northeast India was collected for information on botanical therapies and plant species used for malaria. Sixty-eight plant species belonging to 33 families are used by the people of northeast India for the treatment of malaria. Six plant species, namely, Alstonia scholaris, Coptis teeta, Crotolaria occulta, Ocimum sanctum, Polygala persicariaefolia, Vitex peduncularis, have been reported by more than one worker from different parts of northeast India. The species reported to be used for the treatment of malaria were either found around the vicinity of their habitation or in the forest area of northeast India. The most frequently used plant parts were leaves (33%, roots (31%, and bark and whole plant (12%. The present study has compiled and enlisted the antimalarial plants of northeast India, which would help future workers to find out the suitable antimalarial plants by thorough study.

  16. 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

  17. Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains.

    Science.gov (United States)

    Chugh, Monika; Scheurer, Christian; Sax, Sibylle; Bilsland, Elizabeth; van Schalkwyk, Donelly A; Wicht, Kathryn J; Hofmann, Natalie; Sharma, Anil; Bashyam, Sridevi; Singh, Shivendra; Oliver, Stephen G; Egan, Timothy J; Malhotra, Pawan; Sutherland, Colin J; Beck, Hans-Peter; Wittlin, Sergio; Spangenberg, Thomas; Ding, Xavier C

    2015-02-01

    Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs.

  18. 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.

  19. In vivo antimalarial activities of russelia equisetiformis in plasmodium berghei infected mice

    Directory of Open Access Journals (Sweden)

    O Ojurongbe

    2015-01-01

    Full Text Available The rising problem of resistance to most commonly used antimalarials remains a major challenge in the control of malaria suggesting the need for new antimalarial agents. This work explores the antiplasmodial potential of ethanol extract of Russelia equisetiformis in chloroquine Plasmodium berghei infected mice. Swiss albino mice were intraperitoneally infected with chloroquine-resistant P. berghei (ANKA. Experimental mice were treated for four days consecutively with graded doses of plant extracts and standard antimalarial drugs (artesunate and chloroquine at a dose of 10 mg/kg body weight used as control. The extract showed a dose-dependent activity in the chemosuppression of P. berghei parasites by 31.6, 44.7, 48.4 and 86.5% at doses of 100, 200, 400 and 800 mg/kg, while chloroquine (10 mg/kg and artesunate produced 59.4 and 68.4%, respectively. The extract showed a significant decrease in parasitaemia (P<0.05. The level of parasitemia and decrease in weight in all the treated groups was significantly lower (P<0.05 compared with the infected but untreated mice. The plant extract was devoid of toxicity at the highest dose tested (5000 mg/kg. The study concluded that the ethanol extract of R. equisetiformis possesses antimalarial effect, which supports the folk medicine claim of its use in the treatment of malaria.

  20. 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

  1. 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

  2. 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.

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

    Science.gov (United States)

    Islahudin, Farida; Tindall, Sarah M; Mellor, Ian R; Swift, Karen; Christensen, Hans E M; Fone, Kevin C F; Pleass, Richard J; Ting, Kang-Nee; Avery, Simon V

    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 neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

  4. 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

  5. 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.

  6. Artemisinins: pharmacological actions beyond anti-malarial.

    Science.gov (United States)

    Ho, Wanxing Eugene; Peh, Hong Yong; Chan, Tze Khee; Wong, W S Fred

    2014-04-01

    Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from Artemisia annua L. The anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the Plasmodium species. With its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. Artemisinins have been reported to possess robust inhibitory effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis. Artemisinins have been evaluated in animal models of autoimmune diseases, allergic disorders and septic inflammation. The anti-inflammatory effects of artemisinins have been attributed to the inhibition of Toll-like receptors, Syk tyrosine kinase, phospholipase Cγ, PI3K/Akt, MAPK, STAT-1/3/5, NF-κB, Sp1 and Nrf2/ARE signaling pathways. This review provides a comprehensive update on non-malarial use of artemisinins, modes of action of artemisinins in different disease conditions, and drug development of artemisinins beyond anti-malarial. With the concerted efforts in the novel synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is likely that artemisinin drugs will become a major armamentarium combating a variety of human diseases beyond malaria. PMID:24316259

  7. Design, validation, and absolute sensitivity of a novel test for the molecular detection of avian pneumovirus.

    Science.gov (United States)

    Cecchinato, Mattia; Catelli, Elena; Savage, Carol E; Jones, Richard C; Naylor, Clive J

    2004-11-01

    This study describes attempts to increase and measure sensitivity of molecular tests to detect avian pneumovirus (APV). Polymerase chain reaction (PCR) diagnostic tests were designed for the detection of nucleic acid from an A-type APV genome. The objective was selection of PCR oligonucleotide combinations, which would provide the greatest test sensitivity and thereby enable optimal detection when used for later testing of field materials. Relative and absolute test sensitivities could be determined because of laboratory access to known quantities of purified full-length DNA copies of APV genome derived from the same A-type virus. Four new nested PCR tests were designed in the fusion (F) protein (2 tests), small hydrophobic (SH) protein (1 test), and nucleocapsid (N) protein (1 test) genes and compared with an established test in the attachment (G) protein gene. Known amounts of full-length APV genome were serially diluted 10-fold, and these dilutions were used as templates for the different tests. Sensitivities were found to differ between the tests, the most sensitive being the established G test, which proved able to detect 6,000 copies of the G gene. The G test contained predominantly pyrimidine residues at its 3' termini, and because of this, oligonucleotides for the most sensitive F test were modified to incorporate the same residue types at their 3' termini. This was found to increase sensitivity, so that after full 3' pyrimidine substitutions, the F test became able to detect 600 copies of the F gene.

  8. 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.

  9. [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

  10. 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

  11. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    Directory of Open Access Journals (Sweden)

    Ghosh A

    2014-11-01

    as a test system. Keywords: curcumin, nanotized curcumin, P. berghei, P. falciparum, antimalarial

  12. Malaria and antimalarial plants in Roraima, Brazil.

    Science.gov (United States)

    Milliken, W

    1997-01-01

    One of the numerous problems created by the gold rush which took place in northern Brazil (Roraima State) at the end of the 1980s was a severe epidemic of malaria amongst the indigenous peoples of the region. Worst hit were the Yanomami Indians, who had lived in almost total isolation prior to this event. The problem has been exacerbated by the development of chloroquine-resistant strains of Plasmodium falciparum. In an effort to identify viable alternatives to dependence on western medicine for malaria treatment, a survey was carried out on the local plant species (wild and cultivated) used for this purpose in Roraima. Fieldwork was carried out amongst seven indigenous peoples, as well as with the non-indigenous settlers. Over 90 species were collected, many of which have been cited as used for treatment of malaria and fevers elsewhere. Knowledge of antimalarial plants was found to vary greatly between the communities, and in some cases there was evidence of recent experimentation. Initial screening of plant extracts has shown a high incidence of significant antimalarial activity amongst the species collected. PMID:9204719

  13. 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.

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

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Skare, Lizbet; Lundgren, Lennart;

    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 limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test....

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

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Skare, Lizbet; Lundgren, Lennart;

    2010-01-01

    the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test....

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. On the reliability of sensitivity test methods for submicrometer-sized RDX and HMX particles

    NARCIS (Netherlands)

    Radacsi, N.; Bouma, R.H.B.; Krabbendam-La Haye, E.L.M.; Horst, J.H. ter; Stankiewicz, A.I.; Heijden, A.E.D.M. van der

    2013-01-01

    Submicrometer-sized RDX and HMX crystals were produced by electrospray crystallization and submicrometer-sized RDX crystals were produced by plasma-assisted crystallization. Impact and friction sensitivity tests and ballistic impact chamber tests were performed to determine the product sensitivity.

  2. Test Prioritization based on Change Sensitivity: an Industrial Case Study

    NARCIS (Netherlands)

    Nguyen, Cu; Tonella, Paolo; Vos, Tanja; Condori, Nelly; Mendelson, Bilha; Citron, Daniel; Shehory, Onn

    2014-01-01

    In the context of service-based systems, applications access software services, either home-built or third-party, to orchestrate their functionality. Since such services evolve independently from the applications, the latter need to be tested to make sure that they work properly with the updated or

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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)

  8. Drug Discovery and Development of Antimalarial Agents: Recent Advances.

    Science.gov (United States)

    Thota, Sreekanth; Yerra, Rajeshwar

    2016-01-01

    Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Study of antimalarial activity of chemical constituents from Diospyros quaesita.

    Science.gov (United States)

    Ma, Cui-Ying; Musoke, Sebisubi Fred; Tan, Ghee Teng; Sydara, Kongmany; Bouamanivong, Somsanith; Southavong, Bounhoong; Soejarto, D Doel; Fong, Harry H S; Zhang, Hong-Jie

    2008-11-01

    Bioassay-directed fractionation led to the isolation of seven compounds from a sample of the dried leaves, twigs, and branches of Diospyros quaesita Thw. (Ebenaceae). One of the isolates, betulinic acid 3-caffeate (1), showed in vitro antimalarial activity against Plasmodium falciparum clones D(6) (chloroquine-sensitive) and W(2) (chloroquine-resistant) with IC(50) values of 1.40 and 0.98 microM, respectively. Evaluation of compound 1 in the human oral epidermoid (KB) cancer cell line revealed cytotoxicity at ED(50) of 4.0 microM. In an attempt to reduce the cytotoxicity of 1, the acetylated derivative 1a and betulinic acid (1b) were prepared. Of the seven isolates, diospyrosin (2) was determined to be a new neolignan. In addition to 1, other known compounds isolated in this study were pinoresinol, lariciresinol, N-benzoyl-L-phenylalaninol, scopoletin, and poriferast-5-en-3beta,7alpha-diol. The structure of 2 was elucidated based on spectroscopic data analysis including 1D- and 2D-NMR, and HR-ESI-MS. PMID:19035573

  16. How do antimalarial drugs reach their intracellular targets?

    Directory of Open Access Journals (Sweden)

    Katherine eBasore

    2015-05-01

    Full Text Available Drugs represent the primary treatment available for human malaria, as caused by Plasmodium spp. Currently approved drugs and antimalarial drug leads generally work against parasite enzymes or activities within infected erythrocytes. To reach their specific targets, these chemicals must cross at least three membranes beginning with the host cell membrane. Uptake at each membrane may involve partitioning and diffusion through the lipid bilayer or facilitated transport through channels or carriers. Here, we review the features of available antimalarials and examine whether transporters may be required for their uptake. Our computational analysis suggests that most antimalarials have high intrinsic membrane permeability, obviating the need for uptake via transporters; a subset of compounds appear to require facilitated uptake. We also review parasite and host transporters that may contribute to drug uptake. Broad permeability channels at the erythrocyte and parasitophorous vacuolar membranes of infected cells relax permeability constraints on antimalarial drug design; however, this uptake mechanism is prone to acquired resistance as the parasite may alter channel activity to reduce drug uptake. A better understanding of how antimalarial drugs reach their intracellular targets is critical to prioritizing drug leads for antimalarial development and may reveal new targets for therapeutic intervention.

  17. 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.

  18. 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.

  19. Use of a Simultaneous Sentence Perception Test To Enhance Sensitivity to Ease of Listening.

    Science.gov (United States)

    Mackersie, Carol L.; Boothroyd, Arthur; Prida, Tammy

    2000-01-01

    This study examined whether a divided-attention, sentence recall task was more sensitive to distortion of the speech signal than a conventional focused-attention task with 18 normal hearing listeners. The study concluded that the simultaneous-sentence test, in its present form, is not more sensitive to the effects of peak clipping than is a…

  20. 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;

    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 t...

  1. Antimalarial activity of Bidens pilosa L. (Asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soil.

    Science.gov (United States)

    Andrade-Neto, Valter F; Brandão, Maria G L; Oliveira, Francielda Q; Casali, Vicente W D; Njaine, Brian; Zalis, Mariano G; Oliveira, Luciana A; Krettli, Antoniana U

    2004-08-01

    Bidens pilosa (Asteraceae), a medicinal plant used worldwide, has antimalarial activity as shown in previous work. This study tested ethanol extracts from wild plants collected in three different regions of Brazil and from plants cultivated in various soil conditions. The extracts were active in mice infected with P. berghei: doses of humus enriched soil, were active; but the wild plants were the most active. Analysis using thin layer chromatography demonstrated the presence of flavonoids (compounds considered responsible for the antimalarial activity) in all plants tested, even though at different profiles. Because B. pilosa is proven to be active against P. falciparum drug-resistant parasites in vitro, and in rodent malaria in vivo, it is a good candidate for pre-clinical tests as a phytotherapeutic agent or for chemical isolation of the active compounds with the aim of finding new antimalarial drugs.

  2. Repeated patch testing to nickel during childhood do not induce nickel sensitization

    DEFF Research Database (Denmark)

    Søgaard Christiansen, Elisabeth

    2014-01-01

    Background: Previously, patch test reactivity to nickel sulphate in a cohort of unselected infants tested repeatedly at 3-72 months of age has been reported. A reproducible positive reaction at 12 and 18 months was selected as a sign of nickel sensitivity, provided a patch test with an empty Finn...... chamber was negative. The objective of this study is to follow-up on infants with suspected nickel sensitivity. Methods: A total of 562 infants were included in the cohort and patch tested with nickel sulphate. The 26 children with a positive patch test to nickel sulphate at 12 and 18 months were offered...... repeated patch test to nickel sulphate at 3 (36 months), 6 (72 months) and 14 years of age. Results: At 3 years, 24 of 26 nickel sensitive children were retested and a positive reaction was seen in 7 children, a negative reaction in 16 and 1 child was excluded due to reaction to both nickel and the empty...

  3. 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...

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

    Directory of Open Access Journals (Sweden)

    Arthi K

    2003-01-01

    Full Text Available 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 vancomycin tests are simple, inexpensive and can be used in addition to Gram staining for rapid identification of bacterial cultures.

  5. 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.

  6. 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.

  7. Synthesis of triazol derivatives of lupeol with potential antimalarial activity

    Directory of Open Access Journals (Sweden)

    Tatiane Freitas Borgati

    2012-06-01

    Full Text Available The goal of this project is synthesize and characterization of derivatives of lupeol and evaluated antimalarial activity. Historically, plants are important source of antimalarial medicines, highlighting quinine (1 (Figure 1, an important      alkaloid from the Cinchona calisaya bark. This compound was an important model for cloroquine  synthesis, a drug that was widely used in malaria treatment. In addition, one of the principal medicines used today is artemisinine, isolated from the Chinese plant Artemisia annua L (2 (Figure 1, and their semi synthetic derivatives (artesunate, artemeter, arteter. However, the malaria parasite has already shown resistance    to most of these current drugs and  the search for new candidates is essential. Lupeol (3 (Figura 1 is a compound that occurs in many plant species and discloses antimalarial, antiinflamatoryl and antitumoral activities. Considering its potential as a lead antimalarial molecule, we focused our work in the synthesis of new lupeol derivatives with increased antimalarial activity(scheme 1.

  8. 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. ...

  9. Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests

    NARCIS (Netherlands)

    Arts, G.H.P.; Belgers, J.D.M.; Hoekzema, C.C.; Thissen, J.T.N.M.

    2008-01-01

    The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root e

  10. 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

  11. Evaluation of anti-malarial activity of Artemisia turcomanica and A. kopetdaghensis by cell-free β-hematin formation assay

    Directory of Open Access Journals (Sweden)

    M. Mojarrab

    2016-10-01

    Full Text Available Background and objectives:The plants of genus Artemisia (Asteraceae have been conventionally used for prevention and medication of a number of ailments. In the present research, ten extracts with different polarities from aerial parts of two Artemisia species, A. kopetdaghensis and A. turcomanica were evaluated for their potential anti-malarial properties. Methods: The plant materials were extracted successively with petroleum ether (PE, dichloromethane (DCM, ethyl acetate (EtOAC, ethanol, and ethanol-water (1:1 v/v  by cold maceration method. Cell free β-hematin formation assay were used for assessing anti-malarial activity of obtained extracts. Results: DCM extract of A. kopetdaghensis and PE extract of A. turcomanica showed remarkable anti-malarial activity with IC50 values of 1.04±0.02 mg/mL and 0.90±0.27 mg/mL, respectively, compared to positive control (chloroquine, IC50 0.04±0.01 mg/mL. Conclusion:  It seems that the anti-malarial activity of these extracts might be bound up with the presence of compounds with low or medium polarity; hence, this preliminary test indicated that these potent extracts could be considered for further investigations to find new sources of anti-malarial phytochemicals.

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

    Science.gov (United States)

    Ajaiyeoba, E O; Ogbole, O O; Abiodun, O O; Ashidi, J S; Houghton, P J; Wright, C W

    2013-01-01

    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  μ g/mL (7.4  μ M) and could be a lead for anti-malarial drug discovery. PMID:23970954

  13. 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.

  14. Quinine conjugates and quinine analogues as potential antimalarial agents.

    Science.gov (United States)

    Jones, Rachel A; Panda, Siva S; Hall, C Dennis

    2015-06-01

    Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds.

  15. Artemisinin: An Evolving Antimalarial-Part One

    Directory of Open Access Journals (Sweden)

    Nkereuwem Jonathan Edikpo

    2013-12-01

    Full Text Available This review was conceived with the aim of presenting a compact, yet engaging account of the evolution of artemisinin from its humble and ancient origins as an herbal remedy to a modern chemotherapeutic agent, highlighting its unique pharmacological and toxicological profile and the central position it occupies at present in the battle against malaria. Artemisinin is a sesquiterpene lactone end operoxide with a long and enchanting history. The Chinese had been using concoctions of Artemisia for the treatment of various febrile ailments for close to two millennia. The impetus for its extraction in 1972 from Artemisia annua came from the battlefields of the Vietnamese war of 1965 to 1973 and the political milieu of the Cultural Revolution that encouraged an inward-looking disposition. Owing to solubility problems with the parent compound, artemisinin other semi-synthetic derivatives are now available and include artesunate, artemether, dihydroartemisinin and arteether. Parasiticidal action resides in the endoperoxide moiety which is also primarily responsible for the toxicity of the artemisinin compounds. As a class, they are the most rapidly acting antimalarial chemotherapeutic agents ever in use, reducing initial parasite burden by a factor of 104 per cycle of schizogony. Despite this, high rate of recrudescence occur with monotherapies which necessitates their use in combination with longer acting agents- ACTs. The basis of this high recrudescence is not unrelated to short plasma half-lives, dormancy phenomenon and autoinduction of the metabolizing enzymes. Though safe in humans at recommended dosages, animal studies have continually revealed disturbing side effects most notably, neurotoxicity and, reproductive toxicity manifesting in the twin phenomenon of embryolethality and fetal dysmorphogenesis. In the light of the cautionary tale of thalidomide tragedy, it may not be wise to totally ignore these findings in experimental animals.

  16. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies.

    Directory of Open Access Journals (Sweden)

    Julia Penna-Coutinho

    Full Text Available The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2. The IC(50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use.

  17. Long-term repeatability of the skin prick test is high when supported by history or allergen-sensitivity tests

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Jacobsen, C R; Poulsen, L K;

    2003-01-01

    BACKGROUND: Long-term reproducibility of the skin-prick test (SPT) has been questioned. The aim of the study was to investigate the clinical relevance of SPT changes. METHODS: SPT to 10 common inhalation allergens was performed annually from 1999 to 2001 in 25 nonsensitized and 21 sensitized...

  18. 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)

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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 ...

  4. 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.)

  5. 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

  6. 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......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...

  7. 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

  8. 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)

  9. 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...

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Evaluating the sensitivity and predictive value of tests of recent infection: toxoplasmosis in pregnancy.

    Science.gov (United States)

    Ades, A E

    1991-12-01

    The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it.

  15. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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......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...... sensitization) after orofacial trauma using quantitative sensory testing (QST). Methods: A total of 32 healthy men (16 patients and 16 age-matched control subjects) underwent a battery of quantitative tests adapted to the trigeminal area at baseline and 2, 7, and 30 days following surgical removal of a lower...... impacted third molar. Results: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p

  5. 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;

    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......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...... sensitization) after orofacial trauma using quantitative sensory testing (QST). METHODS: A total of 32 healthy men (16 patients and 16 age-matched control subjects) underwent a battery of quantitative tests adapted to the trigeminal area at baseline and 2, 7, and 30 days following surgical removal of a lower...... impacted third molar. RESULTS: Central sensitization for at least one week was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (p

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

    Directory of Open Access Journals (Sweden)

    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

  7. Sensitivity of Occupant Response Subject to Prescribed Corridors for Impact Testing

    Directory of Open Access Journals (Sweden)

    J.R. Crandall

    1996-01-01

    Full Text Available A technology to study the sensitivity of impact responses to prescribed test conditions is presented. Motor vehicle impacts are used to illustrate the principles of this sensitivity technology. Impact conditions are regulated by specifying either a corridor for the acceleration time history or other test parameters such as velocity change, static crush distance, and pulse duration. By combining a time domain constrained optimization method and a multirigid body dynamics simulator, the upper and lower bounds of occupant responses subject to the regulated corridors were obtained. It was found that these prescribed corridors may be either so wide as to allow extreme variations in occupant response or so narrow that they are physically unrealizable in the laboratory test environment. A new corridor based on specifications for the test parameters of acceleration, velocity. crush distance, and duration for frontal vehicle impacts is given.

  8. Dried whole plant Artemisia annua as an antimalarial therapy.

    Directory of Open Access Journals (Sweden)

    Mostafa A Elfawal

    2012-12-01

    Full Text Available Drugs are primary weapons for reducing malaria in human populations. However emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed. Currently the most effective anti-malarial is artemisinin, which is extracted from the leaves of Artemisia annua. Due to poor pharmacokinetic properties and prudent efforts to curtail resistance to monotherapies, artemisinin is prescribed only in combination with other anti-malarials composing an Artemisinin Combination Therapy (ACT. Low yield in the plant, and the added cost of secondary anti-malarials in the ACT, make artemisinin costly for the developing world. As an alternative, we compared the efficacy of oral delivery of the dried leaves of whole plant (WP A. annua to a comparable dose of pure artemisinin in a rodent malaria model (Plasmodium chabaudi. We found that a single dose of WP (containing 24 mg/kg artemisinin reduces parasitemia more effectively than a comparable dose of purified drug. This increased efficacy may result from a documented 40-fold increase in the bioavailability of artemisinin in the blood of mice fed the whole plant, in comparison to those administered synthetic drug. Synergistic benefits may derive from the presence of other anti-malarial compounds in A. annua. If shown to be clinically efficacious, well-tolerated, and compatible with the public health imperative of forestalling evolution of drug resistance, inexpensive, locally grown and processed A. annua might prove to be an effective addition to the global effort to reduce malaria morbidity and mortality.

  9. 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.

  10. 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

  11. 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 ...

  12. 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...

  13. 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

  14. A new antimalarial agent; effect of extracts of Artemisia diffusa against Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Abdolhossein Rustaiyan

    2009-01-01

    Full Text Available Malaria is one of the most serious health problems in many parts of the world, particularly in Africa and Latin America with a high mortality rate. The situation is further complicated by the spread of drug-resistant parasites in many parts where plasmodium falciparum is endemic. A few alternative drugs are under development, necessitating urgent efforts to identify new classes of antimalarial agents. There is therefore a need to find new, effective and affordable remedies for malaria, including those derived from plants. The clinical utility of the Chinese discovery of artemisinin from the herb Artemisia annua has stimulated much interest in traditional plants as potential sources of new antimalarial drugs. In this study, the antimalarial activity of Artemisia diffusa extracts and the fraction which contains sesquiterpene lactones including Tehranolide, on Plasmodium berghei in vivo on the mice model of malaria was investigated. We did our best to carry out the biological tests as well as the phytochemical investigations from the same collection. It demonstrates that crude extracts of Artemisia diffusa inhibit the growth of Plasmodium berghei in vivo in NMRI mice. The microscopic examination of Giemsa stained slides showed a virtual absence of all blood-stage of murine malaria treated with three concentrations of herbal extracts including 27, 2.7 and 0.27 mg/ml. These observations suggest that the active constituents in the extract may be cytotoxic for P. berghei, thereby inhibiting their development to the erythrocytic stage. The results specifically indicated the inhibitory effects of the A.diffusa crude extracts and the fraction which contains sesquiterpene lactones including Tehranolide, on the developmental stages of P. berghei by decreasing parasitaemia.

  15. 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.

  16. Insecticide species sensitivity distributions: importance of test species selection and relevance to aquatic ecosystems

    NARCIS (Netherlands)

    Maltby, L.; Blake, N.; Brock, T.C.M.; Brink, van den P.J.

    2005-01-01

    Single-species acute toxicity data and (micro)mesocosm data were collated for 16 insecticides. These data were used to investigate the importance of test-species selection in constructing species sensitivity distributions (SSDs) and the ability of estimated hazardous concentrations (HCs) to protect

  17. Rapid, high sensitivity, point-of-care test for cardiac troponin based on optomagnetic biosensor

    NARCIS (Netherlands)

    Dittmer, W.U.; Evers, T.H.; Hardeman, W.M.; Huijnen-Keur, W.M.; Kamps, R.; De Kievit, P.; Neijzen, J.H.M.; Sijbers, M.J.J.; Nieuwenhuis, J.H.; Hefti, M.H.; Dekkers, D.; Martens, M.

    2010-01-01

    BACKGROUND: We present a handheld integrated device based on a novel magnetic-optical technology for the sensitive detection of cardiactroponin I, a biomarker for the positive diagnosis of myocardial infarct, in a finger-prick blood sample. The test can be performed with a turn-around time of 5 min

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

    Directory of Open Access Journals (Sweden)

    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

  19. Direct transfer of HRPII-magnetic bead complexes to malaria rapid diagnostic tests significantly improves test sensitivity

    OpenAIRE

    Ricks, Keersten M.; Adams, Nicholas M.; Thomas F. Scherr; Haselton, Frederick R.; Wright, David W.

    2016-01-01

    Background The characteristic ease of use, rapid time to result, and low cost of malaria rapid diagnostic tests (RDTs) promote their widespread use at the point-of-care for malaria detection and surveillance. However, in many settings, the success of malaria elimination campaigns depends on point-of-care diagnostics with greater sensitivity than currently available RDTs. To address this need, a sample preparation method was developed to deliver more biomarkers onto a malaria RDT by concentrat...

  20. 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

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

    Science.gov (United States)

    Mishra, Kirti; Dash, Aditya P.; Dey, Nrisingha

    2011-01-01

    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. PMID:21760808

  2. 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.

  3. RE-1000 free-piston Stirling engine sensitivity test results. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Schreiber, J.G.; Geng, S.M.; Lorenz, G.V.

    1986-10-01

    The NASA Lewis Research Center has been testing a 1 kW (1.33 hp) free-piston Stirling engine at the NASA Lewis test facilities. The tests performed over the past several years have been on a single cylinder machine known as the RE-1000. The data recorded were to aid in the investigation of the dynamics and thermodynamics of the free-piston Stirling engine. The data are intended to be used primarily for computer code validation. NASA reports TM-82999, TM-83407, and TM-87126 give initial results of the engine tests. The tests were designed to investigate the sensitivity of the engine performance to variations on the mean pressure of the working space, the working fluid used, heater and cooler temperatures, regenerator porosity, power piston mass and displacer dynamics. These tests have now been completed at NASA Lewis. This report presents some of the detailed data collected in the sensitivity tests. In all, 781 data points were recorded. A complete description of the engine and test facility is given. Many of the data can be found in tabular form, while a microfiche containing all of the data points can be requested from NASA Lewis.

  4. 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.

  5. Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity

    Directory of Open Access Journals (Sweden)

    Hongxing Wang

    2013-01-01

    Full Text Available Decoquinate (DQ is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

  6. 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.

  7. Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity.

    Science.gov (United States)

    Wang, Hongxing; Li, Qigui; Reyes, Sean; Zhang, Jing; Xie, Lisa; Melendez, Victor; Hickman, Mark; Kozar, Michael P

    2013-01-01

    Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L- α -phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

  8. 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.

  9. Effect of incubation temperature on the diagnostic sensitivity of the glanders complement fixation test.

    Science.gov (United States)

    Khan, I; Wieler, L H; Saqib, M; Melzer, F; Santana, V L D A; Neubauer, H; Elschner, M C

    2014-12-01

    The complement fixation test (CFT) is the only serological test prescribed by the World Organisation for Animal Health (OIE) for the diagnosis of glanders in international trading of equids. However, false-positive reactions have caused financial losses to the animal owners in the past, and false-negative tests have resulted in the introduction of glanders into healthy equine populations in previously glanders-free areas. Both warm (incubation at 37°C for 1 h) and cold (overnight incubation at 4°C) procedures are recommended by the OIE for serodiagnosis of glanders. In a comparison of the sensitivity and specificity of the two techniques, using the United States Department of Agriculture antigen, warm CFT was found to be significantly less sensitive (56.8%; p glanders but a lower diagnostic specificity has to be accepted. The immunoblot was used as the gold standard.

  10. 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.

  11. 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...

  12. 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

  13. Reliability and sensitivity to change of the timed standing balance test in children with down syndrome

    Directory of Open Access Journals (Sweden)

    Vencita Priyanka Aranha

    2016-01-01

    Full Text Available Objective: To estimate the reliability and sensitivity to change of the timed standing balance test in children with Down syndrome (DS. Methods: It was a nonblinded, comparison study with a convenience sample of subjects consisting of children with DS (n = 9 aged 8–17 years. The main outcome measure was standing balance which was assessed using timed standing balance test, the time required to maintain in four conditions, eyes open static, eyes closed static, eyes open dynamic, and eyes closed dynamic. Results: Relative reliability was excellent for all four conditions with an Interclass Correlation Coefficient (ICC ranging from 0.91 to 0.93. The variation between repeated measurements for each condition was minimal with standard error of measurement (SEM of 0.21–0.59 s, suggestive of excellent absolute reliability. The sensitivity to change as measured by smallest real change (SRC was 1.27 s for eyes open static, 1.63 s for eyes closed static, 0.58 s for eyes open dynamic, and 0.61 s for eyes closed static. Conclusions: Timed standing balance test is an easy to administer test and sensitive to change with strong absolute and relative reliabilities, an important first step in establishing its utility as a clinical balance measure in children with DS.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  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. 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.

  1. 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

  2. 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

  3. 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.

  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. 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

    2016-02-13

    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 (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.

  6. Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.

    Science.gov (United States)

    Floyd, David M; Stein, Philip; Wang, Zheng; Liu, Jian; Castro, Steve; Clark, Julie A; Connelly, Michele; Zhu, Fangyi; Holbrook, Gloria; Matheny, Amy; Sigal, Martina S; Min, Jaeki; Dhinakaran, Rajkumar; Krishnan, Senthil; Bashyum, Sridevi; Knapp, Spencer; Guy, R Kiplin

    2016-09-01

    Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate. PMID:27505686

  7. Synthesis and Antimalarial Activity of Novel Dihydro-Artemisinin Derivatives

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2011-05-01

    Full Text Available The Plasmodium falciparum cysteine protease falcipain-2, one of the most promising targets for antimalarial drug design, plays a key role in parasite survival as a major peptide hydrolase within the hemoglobin degradation pathway. In this work, a series of novel dihydroartemisinin derivatives based on (thiosemicarbazone scaffold were designed and synthesized as potential falcipain-2 inhibitors. The in vitro biological assay indicated that most of the target compounds showed excellent inhibition activity against P. falciparum falcipain-2, with IC50 values in the 0.29–10.63 μM range. Molecular docking studies were performed to investigate the binding affinities and interaction modes for the inhibitors. The preliminary SARs were summarized and could serve as a foundation for further investigation in the development of antimalarial drugs.

  8. Mechanistic Study of the Spiroindolones: A New Class of Antimalarials

    Directory of Open Access Journals (Sweden)

    Thomas H. Keller

    2012-08-01

    Full Text Available During the synthesis of the new antimalarial drug candidate NITD609, a high degree of diastereoselectivity was observed in the Pictet-Spengler reaction. By isolating both the 4E and 4Z imine intermediates, a systematic mechanistic study of the reaction under both kinetic and thermodynamic conditions was conducted. This study provides insight into the source of the diastereoselectivity for this important class of compounds.

  9. 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...

  10. 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...

  11. 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

  12. Rational Design of Proteasome Inhibitors as Antimalarial Drugs.

    Science.gov (United States)

    Le Chapelain, Camille; Groll, Michael

    2016-05-23

    One life, two strategies: Crucial structural differences between the human and the Plasmodium falciparum proteasomes were recently identified. A combination of cryo-EM and functional characterization enabled the design of a selective antimalarial proteasome inhibitor that shows low toxicity in the host. When used with artemisinin, this ligand offers a new approach for the efficient treatment of malaria at all stages of the parasite lifecycle.

  13. Antimalarial diterpene alkaloids from the seeds of Caesalpinia minax.

    Science.gov (United States)

    Ma, Guoxu; Sun, Zhaocui; Sun, Zhonghao; Yuan, Jingquan; Wei, Hua; Yang, Junshan; Wu, Haifeng; Xu, Xudong

    2014-06-01

    Two new diterpene alkaloids, caesalminines A (1) and B (2), possessing a tetracyclic cassane-type furanoditerpenoid skeleton with γ-lactam ring, were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods and ECD calculation. The plausible biosynthetic pathway of caesalminines A and B was proposed. The anti-malarial activity of compounds 1 and 2 is presented with IC50 values of 0.42 and 0.79 μM, respectively.

  14. 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.

  15. 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

  16. 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

  17. Timing and presence of an attachment person affect sensitivity of aggression tests in shelter dogs.

    Science.gov (United States)

    Kis, A; Klausz, B; Persa, E; Miklósi, Á; Gácsi, M

    2014-02-22

    Different test series have been developed and used to measure behaviour in shelter dogs in order to reveal individuals not suitable for re-homing due to their aggressive tendencies. However, behavioural tests previously validated on pet dogs seem to have relatively low predictability in the case of shelter dogs. Here, we investigate the potential effects of (1) timing of the behaviour testing and (2) presence of a human companion on dogs' aggressive behaviour. In Study I, shelter dogs (n=25) showed more aggression when tested in a short test series two weeks after they had been placed in the shelter compared to their responses in the same test performed 1-2 days after arrival. In Study II, the occurrence of aggressive behaviour was more probable in pet dogs (n=50) in the presence than in the absence of their passive owner. We conclude that the sensitivity of aggression tests for shelter dogs can be increased by running the test in the presence of a caretaker, and after some period of acclimatisation to the new environment. This methodology could also provide better chances for successful adoption.

  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. 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.

  20. 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

  1. 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.

  2. A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics

    Directory of Open Access Journals (Sweden)

    T.R. Lavich

    2005-03-01

    Full Text Available It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP test to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51ºC and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 µg/paw and mice (125-500 µg/paw with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, ip inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 µg/paw also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

  3. Dual luminophor pressure-sensitive paint: III. Application to automotive model testing

    Science.gov (United States)

    Gouterman, Martin; Callis, James; Dalton, Larry; Khalil, Gamal; Mébarki, Youssef; Cooper, Kevin R.; Grenier, Michel

    2004-10-01

    Porphyrins play key roles in natural energy conversion systems, including photosynthesis and oxygen transport. Because of their chemical stability, unique optical properties and synthetic versatility, porphyrins are well suited as chemical sensors. One successful application is the use of platinum porphyrin (PtP) in pressure-sensitive paint (PSP). Oxygen in the film quenches luminescence, and oxygen pressure was initially monitored by measuring the ratio of I(wind-off)/I(wind-on). But this ratio is compromised if there is model motion and if the paint layer is inhomogeneous. Furthermore it requires careful monitoring and placement of light sources. Moreover, this method is seriously affected by temperature. The errors caused by model motion and temperature sensitivity are eliminated or greatly reduced using dual luminophor paint. This paper illustrates a successful application of a dual luminophor PSP in auto model testing. The PSP is made from an oxygen sensitive luminophor, Pt tetra(pentafluorophenyl)-porpholactone, which provides Isen, and Mg tetra(pentafluorophenyl)porphine, which provides temperature-sensitive paint (TSP) as the pressure-independent reference. The ratio PSP/TSP in the FIB polymer produced ideal PSP measurements with a very low-temperature dependence of -0.1% °C-1.

  4. Structural features of substituted triazole-linked chalcone derivatives as antimalarial activities against D10 strains ofPlasmodium falciparum:A QSAR approach

    Institute of Scientific and Technical Information of China (English)

    Mukesh C. Sharma

    2015-01-01

    A quantitative structure–activity relationship (QSAR) was performed to analyze antimalarial activities against the D10 strains ofPlasmodium falciparum of triazole-linked chalcone and dienone hybrid derivatives using partial least squares regression coupled with stepwise forward–backward variable selection method. QSAR analyses were performed on the available IC50 D10 strains ofPlasmodium falciparum data based on theoretical molecular descriptors. The QSAR model developed gave good predictive correlation coefficient (r2) of 0.8994, significant cross validated correlation coefficient (q2) of 0.7689,r2 for external test set(p2)redr of 0.8256, coefficient of correlation of predicted data set)(p2sered,r of 0.3276. The model shows that antimalarial activity is greatly affected by donor and electron-withdrawing substituents. The study implicates that chalcone and dienone rings should have strong donor and electron-withdrawing substituents as they increase the activity of chalcone. Results show that the predictive ability of the model is satisfactory, and it can be used for designing similar group of antimalarial compounds. The findings derived from this analysis along with other molecular modeling studies will be helpful in designing of the new potent antimalarial activity of clinical utility.

  5. 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...

  6. 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.

  7. 31P-MRS of skeletal muscle is not a sensitive diagnostic test for mitochondrial myopathy

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Quistorff, Bjørn; Wibrand, Flemming;

    2007-01-01

    diagnostic criterion for MM but the diagnostic strength of this test has not been compared with that of other commonly used diagnostic procedures for MM. To investigate this, we studied seven patients with single, large-scale deletions-, nine with point mutations of mtDNA and 14 healthy subjects, who were...... as 100%, the sensitivity was low (0-63%) and the diagnostic strength of (31)P-MRS was inferior to the other diagnostic tests for MM. Thus, (31)P-MRS should not be a routine test for MM, but may be an important research tool.......Clinical phenotypes of persons with mitochondrial DNA (mtDNA) mutations vary considerably. Therefore, diagnosing mitochondrial myopathy (MM) patients can be challenging and warrants diagnostic guidelines. (31)phosphorous magnetic resonance spectroscopy ((31)P-MRS) have been included as a minor...

  8. 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.

  9. Efficiency test of solar collectors: uncertainty in the estimation of regression parameters and sensitivity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sabatelli, V.; Marano, D.; Braccio, G.; Sharma, V.K. [ENEA CR Trisaia, Solar Energy Lab., Rotondella (Italy)

    2002-11-01

    The results obtained from efficiency tests conducted on a flat plate solar collector, according to the ISO 9806/1 test procedure, have been used to determine the uncertainty in the curve fitting parameters. The said standard, though requiring certain levels of accuracy in the measuring process, does not provide any method to determine the uncertainty of the efficiency curve parameters. The methodology used in the present paper (not provided by the ISO standard) allows solving the above mentioned problem and evaluating not only the parameters and their uncertainties but also the reliability of the test procedure and its goodness toward fitness. In order to evaluate the effects of measurement errors on the values of the uncertainty in estimated parameters, a sensitivity analysis has also been conducted. Strong dependence of some uncertainties, involving a larger accuracy level in the estimation of the measured parameters, is a clear indication of the present investigations. (Author)

  10. 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

  11. Anti-malarial Activities of Two Soil Actinomycete Isolates from Sabah via Inhibition of Glycogen Synthase Kinase 3β.

    Science.gov (United States)

    Dahari, Dhiana Efani; Salleh, Raifana Mohamad; Mahmud, Fauze; Chin, Lee Ping; Embi, Noor; Sidek, Hasidah Mohd

    2016-08-01

    Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection. The present study aims to evaluate whether anti-malarial activities of H11809 and FH025 involve the inhibition of GSK3β. The acetone crude extracts of H11809 and FH025 each exerted strong inhibition on the growth of Plasmodium falciparum 3D7 in vitro with 50% inhibitory concentration (IC50) values of 0.57 ± 0.09 and 1.28 ± 0.11 µg/mL, respectively. The tested extracts exhibited Selectivity Index (SI) values exceeding 10 for the 3D7 strain. Both H11809 and FH025 showed dosage-dependent chemo-suppressive activities in vivo and improved animal survivability compared to non-treated infected mice. Western analysis revealed increased phosphorylation of serine (Ser 9) GSK3β (by 6.79 to 6.83-fold) in liver samples from infected mice treated with H11809 or FH025 compared to samples from non-infected or non-treated infected mice. A compound already identified in H11809 (data not shown), dibutyl phthalate (DBP) showed active anti-plasmodial activity against 3D7 (IC50 4.87 ± 1.26 µg/mL which is equivalent to 17.50 µM) and good chemo-suppressive activity in vivo (60.80% chemo-suppression at 300 mg/kg body weight [bw] dosage). DBP administration also resulted in increased phosphorylation of Ser 9 GSK3β compared to controls. Findings from the present study demonstrate that the potent anti-malarial activities of H11809 and FH025 were mediated via inhibition of host GSK3β. In addition

  12. 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...

  13. 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...

  14. 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.

  15. 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

  16. 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

    and 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...

  17. Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine

    DEFF Research Database (Denmark)

    Casas, Monica Escolà; Hansen, Martin; Krogh, Kristine A;

    2014-01-01

    Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine...... summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs....

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. The in vivo antimalarial activity of methylene blue combined with pyrimethamine, chloroquine and quinine

    Directory of Open Access Journals (Sweden)

    Giovanny Garavito

    2012-09-01

    Full Text Available The effectiveness of methylene blue (MB combined with pyrimethamine (PYR, chloroquine (CQ or quinine (Q was examined in a classical four-day suppressive test against a causative agent of rodent malaria, Plasmodium berghei. A marked potentiation was observed when MB was administered at a non-curative dose of 15 mg/kg/day in combination with PYR (0.19 mg/kg/day or Q (25 mg/kg/day. No synergy was found between MB (15 mg/Kg and CQ (0.75 mg/Kg. Our results suggest that the combination of MB with PYR or Q may improve the efficacy of these currently used antimalarial drugs.

  4. Contaminant Travel Times From the Nevada Test Site to Yucca Mountain: Sensitivity to Porosity

    Science.gov (United States)

    Pohlmann, K. F.; Zhu, J.; Chapman, J. B.; Russell, C. E.; Carroll, R. W.; Shafer, D. S.

    2008-12-01

    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 time frame 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

  5. 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

  6. 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

  7. Simple flow cytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing

    Directory of Open Access Journals (Sweden)

    Grobusch Martin P

    2011-03-01

    Full Text Available Abstract Background Malaria pigment (haemozoin, Hz has been the focus of diverse research efforts. However, identification of Hz-containing leukocytes or parasitized erythrocytes is usually based on microscopy, with inherent limitations. Flow cytometric detection of depolarized Side-Scatter is more accurate and its adaptation to common bench top flow cytometers might allow several applications. These can range from the ex-vivo and in-vitro detection and functional analysis of Hz-containing leukocytes to the detection of parasitized Red-Blood-Cells (pRBCs to assess antimalarial activity. Methods A standard benchtop flow cytometer was adapted to detect depolarized Side-Scatter. Synthetic and Plasmodium falciparum Hz were incubated with whole blood and PBMCs to detect Hz-containing leukocytes and CD16 expression on monocytes. C5BL/6 mice were infected with Plasmodium berghei ANKA or P. berghei NK65 and Hz-containing leukocytes were analysed using CD11b and Gr1 expression. Parasitized RBC from infected mice were identified using anti-Ter119 and SYBR green I and were analysed for depolarized Side Scatter. A highly depolarizing RBC population was monitored in an in-vitro culture incubated with chloroquine or quinine. Results A flow cytometer can be easily adapted to detect depolarized Side-Scatter and thus, intracellular Hz. The detection and counting of Hz containing leukocytes in fresh human or mouse blood, as well as in leukocytes from in-vitro experiments was rapid and easy. Analysis of CD14/CD16 and CD11b/Gr1 monocyte expression in human or mouse blood, in a mixed populations of Hz-containing and non-containing monocytes, appears to show distinct patterns in both types of cells. Hz-containing pRBC and different maturation stages could be detected in blood from infected mice. The analysis of a highly depolarizing population that contained mature pRBC allowed to assess the effect of chloroquine and quinine after only 2 and 4 hours, respectively

  8. 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.

  9. 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...

  10. 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.

  11. 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

    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 ...

  12. 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

  13. 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)

  14. 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...

  15. 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...

  16. 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.

  17. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose–Efficacy Modeling

    Science.gov (United States)

    Le Bihan, Amélie; Angulo-Barturen, Iñigo; Binkert, Christoph; Boss, Christoph; Brun, Reto; Brunner, Ralf; Buchmann, Stephan; Dechering, Koen J.; Delves, Michael; Ewerling, Sonja; Ferrer, Santiago; Fischli, Christoph; Gamo–Benito, Francisco Javier; Heidmann, Bibia; Jiménez-Díaz, María Belén; Leroy, Didier; Martínez, Maria Santos; Meyer, Solange; Moehrle, Joerg J.; Noviyanti, Rintis; Sanz, Laura María; Sauerwein, Robert W.; Scheurer, Christian; Schleiferboeck, Sarah; Sinden, Robert; Snyder, Christopher; Straimer, Judith; Wirjanata, Grennady; Marfurt, Jutta; Weller, Thomas; Clozel, Martine; Wittlin, Sergio

    2016-01-01

    Background Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. Method and Findings The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3–4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11–16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23–39). The compound’s preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as

  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. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Sensitivity analysis and numerical experiments on transient test of compact heat exchanger surfaces

    Institute of Scientific and Technical Information of China (English)

    Hesheng REN; Lingjun LAI; Yongzheng CUI

    2008-01-01

    A single-blow transient testing technique con-sidering the effect of longitudinal heat conduction is sug-gested for determining the average convection heat transfer coefficient of compact heat exchanger surface. By matching the measured outlet fluid temperature vari-ation with similar theoretical curves, the dimensionless longitudinal conduction parameter λ1, the time constant of the inlet fluid temperature τ+, and the number of heat transfer units Ntu can be determined simultaneously using the Levenberg-Marquardt nonlinear parameter estima-tion method. Both sensitivity analysis and numerical experiments with simulated measurements containing random errors show that the method in the present invest-igation provides satisfactory accuracy of the estimated parameter Ntu, which characterizes the heat transfer per-formance of compact heat exchanger surfaces.

  5. 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.

  6. 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.

  7. 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

  8. 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

    2004-02-10

    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 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.

  9. Test and Sensitivity Analysis of Hydrological Modeling in the Coupled WRF-Urban Modeling System

    Science.gov (United States)

    Wang, Z.; yang, J.

    2013-12-01

    Rapid urbanization has emerged as the source of many adverse effects that challenge the environmental sustainability of cities under changing climatic patterns. One essential key to address these challenges is to physically resolve the dynamics of urban-land-atmospheric interactions. To investigate the impact of urbanization on regional climate, physically-based single layer urban canopy model (SLUCM) has been developed and implemented into the Weather Research and Forecasting (WRF) platform. However, due to the lack of realistic representation of urban hydrological processes, simulation of urban climatology by current coupled WRF-SLUCM is inevitably inadequate. Aiming at improving the accuracy of simulations, recently we implemented urban hydrological processes into the model, including (1) anthropogenic latent heat, (2) urban irrigation, (3) evaporation over impervious surface, and (4) urban oasis effect. In addition, we couple the green roof system into the model to verify its capacity in alleviating urban heat island effect at regional scale. Driven by different meteorological forcings, offline tests show that the enhanced model is more accurate in predicting turbulent fluxes arising from built terrains. Though the coupled WRF-SLUCM has been extensively tested against various field measurement datasets, accurate input parameter space needs to be specified for good model performance. As realistic measurements of all input parameters to the modeling framework are rarely possible, understanding the model sensitivity to individual parameters is essential to determine the relative importance of parameter uncertainty to model performance. Thus we further use an advanced Monte Carlo approach to quantify relative sensitivity of input parameters of the hydrological model. In particular, performance of two widely used soil hydraulic models, namely the van Genuchten model (based on generic soil physics) and an empirical model (viz. the CHC model currently adopted in WRF

  10. 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

  11. 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

    on an adriamycin-sensitive Ehrlich ascites tumour and two adriamycin-resistant tumours. Adriamycin caused a dose-related accumulation of tumour cells in the G2 + M phase in the sensitive tumour. Drug concentrations greater than or equal to 100-fold higher were required to induce similar changes in the 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....

  12. 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).

  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. 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).

  15. Antimalarial drug resistance in Bangladesh, 1996-2012.

    Science.gov (United States)

    Haque, Ubydul; Glass, Gregory E; Haque, Waziul; Islam, Nazrul; Roy, Shyamal; Karim, Jahirul; Noedl, Harald

    2013-12-01

    Malaria remains an important health problem in Bangladesh, with approximately 14 million people at risk. Antimalarial drug resistance is a major obstacle to the control of malaria in endemic countries. In 2012, Bangladesh reported an estimated 29 522 malaria episodes, of which 94% were reported as being caused by Plasmodium falciparum. In this study, we reviewed and summarized antimalarial drug resistance data from Bangladesh published until June 2013. We searched published sources for data referring to any type of P. falciparum drug resistance (in vivo, in vitro, or molecular) and found 169 articles published in peer-reviewed journals. Of these, 143 articles were excluded because they did not meet our inclusion criteria. After detailed review of the remaining 26 articles, 14 were selected for evaluation. Published studies indicate that P. falciparum shows varying levels of resistance to chloroquine, mefloquine and sulfadoxine-pyrimethamine. Combination therapy of chloroquine and primaquine has proven ineffective and combinations of sulfadoxine-pyrimethamine with either quinine or chloroquine have also shown poor efficacy. Recent studies indicate that artemisinin derivatives, such as artesunate, remain highly efficacious in treating P. falciparum malaria. Available data suggest that artemisinins, quinine, doxycyline, mefloquine-artesunate and azithromycin-artesunate combination therapy remain efficacious in the treatment of P. falciparum malaria in Bangladesh.

  16. Maximizing antimalarial efficacy and the importance of dosing strategies.

    Science.gov (United States)

    Beeson, James G; Boeuf, Philippe; Fowkes, Freya J I

    2015-05-09

    Artemisinin-based combination therapies (ACTs) are the cornerstone for the treatment of malaria. However, confirmed resistance to artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria treatment and control. Without new drugs to replace artemisinins, it is essential to define dosing strategies that maximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to determine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify other factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by investigators in the Worldwide Antimalarial Resistance Network, have shown high overall efficacy for three widely used ACTs, artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also highlight that suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent study, an analysis of clinical trials of artesunate-amodiaquine, widely used among children in Africa, revealed a superior efficacy for fixed-dose combination tablets compared to loose non-fixed dose combinations. This highlights the benefits of fixed-dose combinations as a practical strategy for ensuring optimal antimalarial dosing and maximizing efficacy. Please see related article: http://www.biomedcentral.com/1741-7015/13/66.

  17. 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

  18. Quantifying the pharmacology of antimalarial drug combination therapy

    Science.gov (United States)

    Hastings, Ian M.; Hodel, Eva Maria; Kay, Katherine

    2016-01-01

    Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs. PMID:27604175

  19. Quantifying the pharmacology of antimalarial drug combination therapy

    Science.gov (United States)

    Hastings, Ian M.; Hodel, Eva Maria; Kay, Katherine

    2016-09-01

    Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs.

  20. 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

  1. Bayesian estimation of sensitivity and specificity of Coxiella burnetii antibody ELISA tests in bovine blood and milk

    DEFF Research Database (Denmark)

    Paul, Suman; Toft, Nils; Agerholm, Jørgen S.;

    2013-01-01

    Serological tests for Coxiella burnetii (the causative agent of Q fever) antibodies are usually based on enzyme linked immunosorbent assay (ELISA) although this method is not thoroughly evaluated. The objective of this study was to determine the sensitivity and specificity of an ELISA for detection...... of the ELISA methods on milk and blood were equal at 0.99. No conditional dependence was observed between the specificity estimates of the two test methods. However, the sensitivity estimates of both tests were significantly reduced when conditional covariances ≥40 were used. Collection of milk samples from...... to positive (S/P) cut-off of 40 for both blood and milk ELISAs. At this cut-off, sensitivity of milk ELISA was 0.86 (95% posterior credibility interval [PCI] [0.76; 0.96]). This was slightly but insignificantly higher than sensitivity of blood ELISA (0.84; 95% PCI [0.75; 0.93]). The specificity estimates...

  2. 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.

  3. Application of KRL test to assess total antioxidant activity in pigs: sensitivity to dietary antioxidants.

    Science.gov (United States)

    Rossi, Raffaella; Pastorelli, Grazia; Corino, Carlo

    2013-04-01

    The application of Kit Radicaux Libres (KRL) test to assess total blood antioxidant activity in pigs was evaluated. The KRL has been validated and is widely used in humans for assessing the effectiveness of natural or pharmaceutical treatments, and in vitro to evaluate the antioxidant activities of natural or synthetic antioxidants. In this study the sensitivity of the KRL test in assessing the effectiveness of dietary antioxidant supplementation (vitamin E and plant extract) was evaluated in two different phases of pig breeding. The first trial, in post-weaned piglets (40 piglets/group) fed dietary vitamin E supplementation for 60 days, indicated that there was a higher total antioxidant activity (P=0.032) of whole blood and of red blood cells (P=0.001) than for control pigs. The second trial indicated that long-term supplementation of water soluble plant extract (20 pigs/group) from the leaves of Verbenaceae (Lippia spp.) tended (P=0.091) to increase antioxidant activity in the whole blood of treated, rather than control pigs. These results indicate that the KRL might be recommended as one of efficient means for evaluating antioxidant activity of dietary ingredients fed to pigs.

  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. 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

  6. A combination of the leaves and tuber of Icacina senegalensis A. Juss (Icacinaceae improves the antimalarial activity of the plant in mice

    Directory of Open Access Journals (Sweden)

    Esien David-Oku

    2015-10-01

    Full Text Available Objective: To investigate the possibility of increased antimalarial activity of Icacina senegalensis A. Juss (Icacinaceae upon a combination of its leaves and tubers against Plasmodium berghei malaria in mice. Methods: Chloroquine sensitive ANKA clones of Plasmodium 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 tuberleaf 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 of Icacina 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.

  7. 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.

  8. 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.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Harrington, J.F.; Horseman, S.T. [British Geological Survey, Nottingham (United Kingdom)

    2003-01-01

    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

  11. 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

  12. Genotoxicity investigation of ELF-magnetic fields in Salmonella typhimurium with the sensitive SOS-based VITOTOX test

    NARCIS (Netherlands)

    Verschaeve, Luc; Anthonissen, Roel; Grudniewska, Magda; Wudarski, Jakub; Gevaert, Lieven; Maes, Annemarie

    2011-01-01

    We performed a genotoxicity investigation of extremely low-frequency (ELF) magnetic fields (MFs, 50 Hz, 100 and 500 µT, 1 and 2 h exposure) alone and in combination with known chemical mutagens using the VITOTOX test. This test is a very sensitive reporter assay of Salmonella typhimurium bacteria ba

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

    Science.gov (United States)

    Starkweather, Angela R; Heineman, Amy; Storey, Shannon; Rubia, Gil; Lyon, Debra E; Greenspan, Joel; Dorsey, Susan G

    2016-02-01

    Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population.

  18. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

    Science.gov (United States)

    White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

    2016-09-22

    Background KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. Methods We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Results Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. Conclusions KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P

  19. 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.

  20. 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....

  1. 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...

  2. Sensitivity of surveillance testing for multidrug-resistant Gram-negative bacteria in the intensive care unit.

    Science.gov (United States)

    Ridgway, Jessica P; Peterson, Lance R; Thomson, Richard B; Miller, Becky A; Wright, Marc-Oliver; Schora, Donna M; Robicsek, Ari

    2014-11-01

    We tested intensive care unit patients for colonization with multidrug-resistant Gram-negative bacilli (MDR GNB) and compared the results with those of concurrent clinical cultures. The sensitivity of the surveillance test for detecting MDR GNB was 58.8% (95% confidence interval, 48.6 to 68.5%). Among 133 patients with positive surveillance tests, 61% had no prior clinical culture with MDR GNB.

  3. 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

  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. 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

  6. 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)

  7. 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

  8. 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

  9. 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.

  10. Immunochemical Analysis of the Antimalarial Drugs Artemisinin and Artesunate

    Directory of Open Access Journals (Sweden)

    Hiroyuki Tanaka

    2012-11-01

    Full Text Available We prepared a monoclonal antibody (mAb 1C1 showing specificity for artemisinin (AM and artesunate (AS, and we developed an indirect competitive enzyme-linked immunosorbent assay (icELISA using this novel mAb. Moreover, we prepared a recombinant antibody derived from mAb 1C1 in order to overcome insufficient mAb production by hybridoma culture. A recombinant antigen-binding fragment (Fab was easily constructed using antibody manipulation technologies and was produced by microorganisms in high yield. We herein review immunochemical approaches for analysis of the antimalarial drugs AM and AS that were able to yield analysis results for multiple samples in a short period of time using simple and reliable protocols.

  11. 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)

  12. 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.;

    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...

  13. 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

  14. 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

  15. Plot-scale testing and sensitivity analysis of Be7 based soil erosion conversion models

    Science.gov (United States)

    Taylor, Alex; Abdelli, Wahid; Barri, Bashar Al; Iurian, Andra; Gaspar, Leticia; Mabit, Lionel; Millward, Geoff; Ryken, Nick; Blake, Will

    2016-04-01

    an estimated amount of sediment delivered from the plot for comparison with the true mass captured. Sensitivity analysis was undertaken to evaluate the influence of (1) variability in Be-7 depth distribution, (2) selection of particle size correction factors and (3) potential loss of Be-7 in overland flow after SOF initiation on model output. Order of magnitude differences in sediment export estimates across the tested scenarios underpins the critical need for adequately addressing sources of uncertainty in experimental design and sampling programmes. Recommendations are made to improve methodological accuracy and confidence in model outputs.

  16. 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

  17. 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...

  18. 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...

  19. 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. ...

  20. 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...... levels suppressed the lymphocytes' proliferation, but not their IL-2 production. All three quinolines suppressed the proliferation of lymphocytes, but not equally, with mefloquine having the strongest effect. Quinine suppressed the growth at therapeutic concentrations. The IL-2 production was suppressed...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  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. 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

  7. Sensitivity of SWOT discharge algorithm to measurement errors: Testing on the Sacramento River

    Science.gov (United States)

    Durand, Micheal; Andreadis, Konstantinos; Yoon, Yeosang; Rodriguez, Ernesto

    2013-04-01

    Scheduled for launch in 2019, the Surface Water and Ocean Topography (SWOT) satellite mission will utilize a Ka-band radar interferometer to measure river heights, widths, and slopes, globally, as well as characterize storage change in lakes and ocean surface dynamics with a spatial resolution ranging from 10 - 70 m, with temporal revisits on the order of a week. A discharge algorithm has been formulated to solve the inverse problem of characterizing river bathymetry and the roughness coefficient from SWOT observations. The algorithm uses a Bayesian Markov Chain estimation approach, treats rivers as sets of interconnected reaches (typically 5 km - 10 km in length), and produces best estimates of river bathymetry, roughness coefficient, and discharge, given SWOT observables. AirSWOT (the airborne version of SWOT) consists of a radar interferometer similar to SWOT, but mounted aboard an aircraft. AirSWOT spatial resolution will range from 1 - 35 m. In early 2013, AirSWOT will perform several flights over the Sacramento River, capturing river height, width, and slope at several different flow conditions. The Sacramento River presents an excellent target given that the river includes some stretches heavily affected by management (diversions, bypasses, etc.). AirSWOT measurements will be used to validate SWOT observation performance, but are also a unique opportunity for testing and demonstrating the capabilities and limitations of the discharge algorithm. This study uses HEC-RAS simulations of the Sacramento River to first, characterize expected discharge algorithm accuracy on the Sacramento River, and second to explore the required AirSWOT measurements needed to perform a successful inverse with the discharge algorithm. We focus on the sensitivity of the algorithm accuracy to the uncertainty in AirSWOT measurements of height, width, and slope.

  8. 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

  9. 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

  10. In Vitro and In Vivo Antimalarial Activity of Ficus thonningii Blume (Moraceae and Lophira alata Banks (Ochnaceae, Identified from the Ethnomedicine of the Nigerian Middle Belt

    Directory of Open Access Journals (Sweden)

    M. O. Falade

    2014-01-01

    Full Text Available Drug resistance in Plasmodium falciparum requires that new drugs must be developed. Plants are a potential source for drug discovery and development. Two plants that used to treat febrile illnesses in Nigeria were tested for in vitro and in vivo antimalarial activity and cytotoxicity in cancer cell lines. Methanol, hexane, and ethyl acetate leaf extracts of Ficus thonningii and Lophira alata were active in in vitro assays against P. falciparum NF54 (sensitive and K1 (multiresistant strains. Hexane extracts of F. thonningii and L. alata were the most effective extracts in in vitro assays with IC50 of 2.7±1.6 μg/mL and 2.5±0.3 μg/mL for NF54 and 10.4±1.6 μg/mL and 2.5±2.1 μg/mL for K1 strain. All extracts were nontoxic in cytotoxicity assays against KB human cell line with IC50 of over 20 μg/mL, demonstrating selectivity against P. falciparum. In vivo analysis shows that hexane extracts of both plants reduced parasitaemia. At the maximum dose tested, L. alata had a 74.4% reduction of parasitaemia while F. thonningii had a reduction of 84.5%, both extracts prolonged animal survival in mice infected with P. berghei NK65 when compared with vehicle treated controls. The antiplasmodial activity observed justifies the use of both plants in treating febrile conditions.

  11. 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

  12. 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)…

  13. 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

  14. 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.

  15. 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

  16. 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...

  17. Longevity Tests of High-Sensitivity BD-PND Bubble Dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Radev, R; Carlberg, E

    2002-07-09

    Medium- and very-high-sensitivity neutron bubble dosimeters (BD-PNDs) made by Bubble Technology Industries (BTI) were used to study the life span of such dosimeters in a standard setup with a {sup 252}Cf source. Although data on the longevity of bubble dosimeters with low and medium sensitivity exist, such data for dosimeters with high and very high sensitivity are not readily available. The manufacturer guarantees optimum dosimeter performance for 3 months after receipt. However, it is important to know the change in the dosimeters' characteristics with time, especially after the first 3 months. The long-term performance of four sets of very high sensitivity and one set of medium-sensitivity bubble dosimeters was examined for periods of up to 13 months. During that time, the detectors were exposed and reset more than 20 times. Although departures from initial detection sensitivity were observed in several cases, the detectors indicated a significantly longer life span than stated in the manufacturer's warranty. In addition, the change in the number of bubbles and in evaluated neutron dose as a function of the time from the end of exposure until the dosimeters were read was investigated.

  18. 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.

  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. 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.

  2. Structure-activity relationship of anti-malarial spongean peroxides having a 3-methoxy-1,2-dioxane structure.

    Science.gov (United States)

    Kawanishi, Motoyuki; Kotoku, Naoyuki; Itagaki, Sawako; Horii, Toshihiro; Kobayashi, Motomasa

    2004-10-15

    In order to study the structure-activity relationship of anti-malarial spongean peroxides, several analogues concerning with the 6-methoxyacetyl moiety and the 3-pentyl residue in methyl 2-(3-methoxy-3-pentyl-1,2-dioxan-6-yl)acetate were synthesized and evaluated for anti-malarial activity. The tert-butyl ester analogue 14 showed stability in mouse serum and a high selectivity index against the malaria parasite, Plasmodium falciparum, and the citronellyl analogue 31 exhibited the strongest in vitro anti-malarial activity among them, and the imidazole analogue 25 showed desirable in vivo anti-malarial activity against P. berghei infected mice. PMID:15388157

  3. The sensitivity of laboratory tests assessing driving related skills to dose-related impairment of alcohol: A literature review.

    Science.gov (United States)

    Jongen, S; Vuurman, E F P M; Ramaekers, J G; Vermeeren, A

    2016-04-01

    Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. PMID:26802474

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  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. Serological tests in leprosy. The sensitivity, specificity and predictive value of ELISA tests based on phenolic glycolipid antigens, and the implications for their use in epidemiological studies.

    Science.gov (United States)

    Burgess, P J; Fine, P E; Ponnighaus, J M; Draper, C

    1988-08-01

    This paper examines the sensitivity and specificity of two ELISA assays for IgM antibodies to Mycobacterium leprae, one employing natural phenolic glycolipid and the other employing a synthetic disaccharide glycoconjugate as antigen. Estimates of sensitivity and specificity are derived, based on a panel of sera from leprosy cases in Malawi and various non-leprosy controls from the UK. Though both assays were able to identify a high proportion of multibacillary patients, neither was able to detect a high proportion of paucibacillary patients without considerable loss of specificity. The implications of the inverse relationship between sensitivity and specificity are discussed with reference to the predictive value of such tests in such areas as Malawi, where the large majority of cases are paucibacillary.

  14. Perspective for the production of antimalarial drugs in Brazil.

    Science.gov (United States)

    Gilbert, B

    1992-01-01

    There appears to be no chemical manufacture of antimalarial drugs in Brazil. Technology at the laboratory process level has been developed for chloroquine, mefloquine, pyrimethamine and cycloguanil, but not perfected nor scaled-up, largely for economic reasons and market uncertainty. Development of primaquine has been contracted but it will run into the same difficulty. Manufacturing capacity for sulfadoxine was registered in the SDI by Roche. A project to produce artemisinine and its derivatives is under way at UNICAMP-CPQBA but is hampered by low content in the plant. Proguanil could be produced easily, but apparently no attempt has been made to do so. Quinine is imported on a large scale mostly for soft-drink production. Since malarial treatment falls largely within the responsibility of the Government health authorities, manufacture of drugs in Brazil will depend on an assured medium-term purchase order made to a potential local manufacturer, since competition in the world market is scarcely viable at the present moment.

  15. Targeting histone deacetylase inhibitors for anti-malarial therapy.

    Science.gov (United States)

    Andrews, Katherine T; Tran, Thanh N; Wheatley, Nicole C; Fairlie, David P

    2009-01-01

    It is now clear that histone acetylation plays key roles in regulating gene transcription in both eukaryotes and prokaryotes, the acetylated form inducing gene expression while deacetylation silences genes. Recent studies have identified roles for histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) in a number of parasites including Entamoeba histolytica, Toxoplasma gondii, Schistosoma mansoni, Cryptosporidium sp., Leishmania donovani, Neospora caninum, and Plasmodium falciparum. Here we survey fairly limited efforts to date in profiling antimalarial activities of HDAC inhibitors, showing that such compounds are potent inhibitors of the growth of P. falciparum in vitro and in vivo. Most of the compounds evaluated so far have borne a zinc-binding hydroxamate group that tends to be metabolized in vivo, and thus new zinc-binding groups need to be incorporated into second generation inhibitors in order to mask the catalytic zinc in the active site of HDACs. Also the development of compounds that are selective for parasitic HDACs over mammalian HDACs is still in relative infancy and it will take some time to derive antiparasitic HDAC inhibitor compounds with minimal toxicity for the host and acceptable pharmacokinetic and pharmacodynamic profiles for human treatment. Nevertheless, results to date suggest that HDAC inhibitor development represents a promising new approach to the potential treatment of parasitic infections, including those induced by malaria protozoa, and may offer new therapeutic targets within increasingly drug-resistant malarial parasites. PMID:19355992

  16. 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

  17. Distinguishing between learning and motivation in behavioral tests of the reinforcement sensitivity theory of personality.

    Science.gov (United States)

    Smillie, Luke D; Dalgleish, Len I; Jackson, Chris J

    2007-04-01

    According to Gray's (1973) Reinforcement Sensitivity Theory (RST), a Behavioral Inhibition System (BIS) and a Behavioral Activation System (BAS) mediate effects of goal conflict and reward on behavior. BIS functioning has been linked with individual differences in trait anxiety and BAS functioning with individual differences in trait impulsivity. In this article, it is argued that behavioral outputs of the BIS and BAS can be distinguished in terms of learning and motivation processes and that these can be operationalized using the Signal Detection Theory measures of response-sensitivity and response-bias. In Experiment 1, two measures of BIS-reactivity predicted increased response-sensitivity under goal conflict, whereas one measure of BAS-reactivity predicted increased response-sensitivity under reward. In Experiment 2, two measures of BIS-reactivity predicted response-bias under goal conflict, whereas a measure of BAS-reactivity predicted motivation response-bias under reward. In both experiments, impulsivity measures did not predict criteria for BAS-reactivity as traditionally predicted by RST.

  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...

  19. Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach.

    Science.gov (United States)

    Sheynin, Jony; Moustafa, Ahmed A; Beck, Kevin D; Servatius, Richard J; Myers, Catherine E

    2015-04-15

    Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during "non-threat" periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities.

  20. Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach.

    Science.gov (United States)

    Sheynin, Jony; Moustafa, Ahmed A; Beck, Kevin D; Servatius, Richard J; Myers, Catherine E

    2015-04-15

    Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during "non-threat" periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities. PMID:25639540

  1. 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.

  2. Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

    Science.gov (United States)

    Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

    Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

  3. 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

  4. 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.

  5. 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 ...

  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. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  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. IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

    Science.gov (United States)

    2016-01-01

    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

  14. In vitro sensitivity of Plasmodium falciparum field isolates to extracts from Cameroonian Annonaceae plants.

    Science.gov (United States)

    Kemgne, Eugénie Aimée Madiesse; Mbacham, Wilfred Fon; Boyom, Fabrice Fekam; Zollo, Paul Henri Amvam; Tsamo, Etienne; Rosenthal, Philip J

    2012-01-01

    In a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three Annonaceae species, Uvariopsis congolana (leaf, stem), Polyalthia oliveri (stem bark), and Enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. The extracts were prepared from 500 g of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. Evaluation of the activity of fractions in vitro against field isolates of the malaria parasite Plasmodium falciparum showed that acetogenin-rich fractions and interface precipitates were the most potent, with IC(50) values ranging from 0.05 to 8.09 μg/ml. Sensitivity of parasite isolates to plant extracts varied greatly, with over 100-fold difference from isolate to isolate in some cases. The active acetogenin-rich fractions and interface precipitates were assessed in combination with chloroquine in the same conditions, and showed additive interaction in the huge majority of cases. Synergistic interactions were found in some cases with acetogenin-rich fractions. Acute toxicity of promising fractions was evaluated through oral administration in Swiss albino mice. Tested fractions appeared to be safe, with LD(50) values higher than 2 g/kg. In summary, acetogenin-rich fractions from Annonaceae species showed high potency against P. falciparum field isolates and safety by oral administration in mice, supporting their detailed investigation for antimalarial drug discovery.

  15. Parametric sensitivity analysis of a test cell thermal model using spectral analysis

    CERN Document Server

    Mara, Thierry Alex; Garde, François

    2012-01-01

    The paper deals with an empirical validation of a building thermal model. We put the emphasis on sensitivity analysis and on research of inputs/residual correlation to improve our model. In this article, we apply a sensitivity analysis technique in the frequency domain to point out the more important parameters of the model. Then, we compare measured and predicted data of indoor dry-air temperature. When the model is not accurate enough, recourse to time-frequency analysis is of great help to identify the inputs responsible for the major part of error. In our approach, two samples of experimental data are required. The first one is used to calibrate our model the second one to really validate the optimized model.

  16. 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

  17. 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)

  18. 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...

  19. 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.

  20. Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory.

    Science.gov (United States)

    Richards, J S; Arias Vásquez, A; von Rhein, D; van der Meer, D; Franke, B; Hoekstra, P J; Heslenfeld, D J; Oosterlaan, J; Faraone, S V; Buitelaar, J K; Hartman, C A

    2016-01-01

    Little is known about the causes of individual differences in reward sensitivity. We investigated gene-environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes. PMID:27045841

  1. 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.

  2. Sensitivity of a point of care tick-test for the development of Lyme borreliosis

    NARCIS (Netherlands)

    Sprong, H.; Leeuwen, van A.D.; Fonville, M.; Harms, M.; Vliet, van A.J.H.; Pelt, van W.; Ferreira, J.A.; Wijngaard, van den C.C.

    2013-01-01

    Background: A commercially available self-test for the detection of Borrelia burgdorferi sensu lato in ticks was evaluated for its ability to predict erythema migrans formation. Findings: The self-test was performed on 127 Ixodes ricinus from 122 humans that reported tick bites at enrolment and occu

  3. Sensitivity of continuous performance test (CPT) at age 14years to developmental methylmercury exposure

    DEFF Research Database (Denmark)

    Julvez, Jordi; Debes, Frodi; Weihe, Pal;

    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...

  4. 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.

  5. 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

  6. 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...

  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.; 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...

  8. In vitro antimalarial activity and cytotoxicity of some selected cuban medicinal plants Actividad antimalárica in vitro y citotoxicidad de algunas plantas medicinales Cubanas seleccionadas

    Directory of Open Access Journals (Sweden)

    Aymé Fernández-Calienes Valdés

    2010-08-01

    Full Text Available Terrestrial plants have been demonstrated to be sources of antimalarial compounds. In Cuba, little is known about antimalarial potentials of plant species used as medicinals. For that reason, we evaluated the antimalarial activity of 14 plant species used in Cuba as antimalarial, antipyretic and/or antiparasitic. Hydroalcoholic extracts were prepared and tested in vitro for the antimalarial activity against Plasmodium falciparum Ghana strain and over human cell line MRC-5 to determine cytotoxicity. Parasite multiplication was determined microscopically by the direct count of Giemsa stained parasites. A colorimetric assay was used to quantify cytotoxicity. Nine extracts showed IC50 values lower than 100 µg/mL against P. falciparum, four extracts were classified as marginally active (SI 10. B. vulgaris showed the most potent and specific antiplasmodial action (IC50 = 4.7 µg/mL, SI = 28.9. Phytochemical characterization of active extracts confirmed the presence of triterpenoids in B. vulgaris and polar compounds with phenol free groups and fluorescent metabolites in both extracts as major phytocompounds, by thin layer chromatography. In conclusion, antimalarial use of B. vulgaris and P. hysterophorus was validated. B. vulgaris and P. granatum extracts were selected for follow-up because of their strong antimalarial activity.Las plantas terrestres han demostrado ser fuentes de compuestos antimaláricos. En Cuba, el conocimiento sobre el potencial antimalárico de las plantas medicinales es escaso. Por esta razón, evaluamos la actividad antimalárica de 14 especies de plantas usadas en Cuba como antimaláricas, antipiréticas y/o antiparasitarias. Se prepararon extractos hidroalcohólicos y se probaron in vitro frente a la cepa Ghana de Plasmodium falciparum para la actividad antimalárica y frente a la línea celular humana MRC-5 para determinar citotoxicidad. La multiplicación de los parásitos se determinó microscópicamente mediante el

  9. 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.

  10. Evaluation of Five Tests for Sensitivity to Functional Deficits following Cervical or Thoracic Dorsal Column Transection in the Rat.

    Directory of Open Access Journals (Sweden)

    Nitish D Fagoe

    Full Text Available The dorsal column lesion model of spinal cord injury targets sensory fibres which originate from the dorsal root ganglia and ascend in the dorsal funiculus. It has the advantages that fibres can be specifically traced from the sciatic nerve, verifiably complete lesions can be performed of the labelled fibres, and it can be used to study sprouting in the central nervous system from the conditioning lesion effect. However, functional deficits from this type of lesion are mild, making assessment of experimental treatment-induced functional recovery difficult. Here, five functional tests were compared for their sensitivity to functional deficits, and hence their suitability to reliably measure recovery of function after dorsal column injury. We assessed the tape removal test, the rope crossing test, CatWalk gait analysis, and the horizontal ladder, and introduce a new test, the inclined rolling ladder. Animals with dorsal column injuries at C4 or T7 level were compared to sham-operated animals for a duration of eight weeks. As well as comparing groups at individual timepoints we also compared the longitudinal data over the whole time course with linear mixed models (LMMs, and for tests where steps are scored as success/error, using generalized LMMs for binomial data. Although, generally, function recovered to sham levels within 2-6 weeks, in most tests we were able to detect significant deficits with whole time-course comparisons. On the horizontal ladder deficits were detected until 5-6 weeks. With the new inclined rolling ladder functional deficits were somewhat more consistent over the testing period and appeared to last for 6-7 weeks. Of the CatWalk parameters base of support was sensitive to cervical and thoracic lesions while hind-paw print-width was affected by cervical lesion only. The inclined rolling ladder test in combination with the horizontal ladder and the CatWalk may prove useful to monitor functional recovery after experimental

  11. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history...

  12. 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

  13. The anti-malarial artesunate is also active against cancer.

    Science.gov (United States)

    Efferth, T; Dunstan, H; Sauerbrey, A; Miyachi, H; Chitambar, C R

    2001-04-01

    Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy. PMID:11251172

  14. 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

  15. 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...

  16. 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

  17. 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.

  18. 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...

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi

    Directory of Open Access Journals (Sweden)

    Dismas Baza

    2011-02-01

    Full Text Available Abstract Background Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Methods Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO, a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment of AS-AQ, quinine and other anti-malarials were calculated. Results Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9% compared to public (4.2% and NGO (0% outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu. Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu, private and NGO sectors (both US$1.61 or 2,000 FBu. Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors

  6. Retinal toxicity induced by antimalarial drugs: literature review and case report.

    Science.gov (United States)

    Garza-Leon, Manuel; Flores-Alvarado, Diana Elsa; Muñoz-Bravo, Juan Manuel

    2016-01-01

    Antimalarial drugs are widely used in several countries for control of rheumatologic diseases such as systemic lupus erythematosus and rheumatoid arthritis. They are still used in Mexico because of their low cost and few secondary effects, most of which are mild and reversible. Even so, at an ophthalmological level, they could produce irreversible visual damage, which is why it is important to have ophthalmological evaluation and proper follow up. We present a clinical case as an example of characteristic ophthalmological findings as well as risk factors for retinal toxicity. We then discuss guidelines for diagnosis and follow up of patients who use antimalarial drugs for the treatment of rheumatologic illnesses. PMID:27391903

  7. Abandoning presumptive antimalarial treatment for febrile children aged less than five years--a case of running before we can walk?

    Directory of Open Access Journals (Sweden)

    Mike English

    2009-01-01

    Full Text Available BACKGROUND TO THE DEBATE: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five.

  8. Sensitivity Test of 1-D Analysis for MSLB in 3{sup rd} ATLAS Domestic Standard Problem (DSP-03)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.; Huh, J. S.; Park, Y. S.; Bae, B. U.; Kang, K. H.; Choi, K. Y. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, J. J. [KEPCO E and C, Daejeon (Korea, Republic of); Lee, J. S. [KINS, Daejeon (Korea, Republic of); Son, H. H. [Hanyang University, Seoul (Korea, Republic of); Ha, T. W. [Pusan National University, Busan (Korea, Republic of); Kim, J. I. [DOOSAN Heavy Industry, Hwasung (Korea, Republic of)

    2015-10-15

    This exercise aims at effective utilization of integral effect database obtained from the ATLAS, establishment of cooperation framework among the domestic nuclear industry, better understanding of thermal hydraulic phenomena, and investigation of the possible limitation of the existing best-estimate safety analysis codes. As the DSP exercise, 100% Guillotine Break of Steam line without LOOP at zero power condition (- 8%) was determined. In this paper, the activity for sensitivity test of 1-D analysis for SLB transient experiment is described. Six domestic organizations (KEPCO E and C, KINS, Hanyang University, Pusan National University, DOOSAN Heavy Industry, and KAERI) joined and done the 1-D analysis using MARS-KS in an open calculation environment. This group modified the input decks (node modification, combination of models, and etc.) to predict thermal hydraulic phenomena in the ATLAS system. This group also analyzed the sensitivity by modifications to suggest some guide lines for users who makes input deck. Some sensitivity tests of 1-D analysis for SLB transient experiment were done as activity of DSP-03.

  9. 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

  10. Attachment and parental divorce: a test of the diffusion and sensitive period hypotheses.

    Science.gov (United States)

    Fraley, R Chris; Heffernan, Marie E

    2013-09-01

    One of the assumptions of attachment theory is that disruptions in parental relationships are prospectively related to insecure attachment patterns in adulthood. The majority of research that has evaluated this hypothesis, however, has been based on retrospective reports of the quality of relationships with parents-research that is subject to retrospective biases. In the present research, the authors examined the impact of parental divorce-an event that can be assessed relatively objectively-on attachment patterns in adulthood across two samples. The data indicate that parental divorce has selective rather than diffuse implications for insecure attachment. Namely, parental divorce was more strongly related to insecure relationships with parents in adulthood than insecure relationships with romantic partners or friends. In addition, parental insecurity was most pronounced when parental divorce took place in early childhood. This finding is consistent with hypotheses about sensitive periods in attachment development.

  11. 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

  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. 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

  14. Sensitivity during the forced swim test is a key factor in evaluating the antidepressant effects of abscisic acid in mice.

    Science.gov (United States)

    Qi, Cong-Cong; Shu, Yu-Mian; Chen, Fang-Han; Ding, Yu-Qiang; Zhou, Jiang-Ning

    2016-03-01

    Abscisic acid (ABA), a crucial phytohormone, is distributed in the brains of mammals and has been shown to have antidepressant effects in the chronic unpredictable mild stress test. The forced swim test (FST) is another animal model that can be used to assess antidepressant-like behavior in rodents. Here, we report that the antidepressant effects of ABA are associated with sensitivities to the FST in mice. Based on mean immobility in the 5-min forced swim pre-test, ICR mice were divided into short immobility mice (SIM) and long immobility mice (LIM) substrains. FST was carried out 8 days after drug administration. Learned helplessness, as shown by increased immobility, was only observed in SIM substrain and could be prevented by an 8-day ABA treatment. Our results show that ABA has antidepressant effects in SIM substrain and suggest that mice with learned helplessness might be more suitable for screening potential antidepressant drugs.

  15. 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,…

  16. Rasch Modeling of Revised Token Test Performance: Validity and Sensitivity to Change

    Science.gov (United States)

    Hula, William; Doyle, Patrick J.; McNeil, Malcolm R.; Mikolic, Joseph M.

    2006-01-01

    The purpose of this research was to examine the validity of the 55-item Revised Token Test (RTT) and to compare traditional and Rasch-based scores in their ability to detect group differences and change over time. The 55-item RTT was administered to 108 left- and right-hemisphere stroke survivors, and the data were submitted to Rasch analysis.…

  17. 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

  18. Testing taste sensitivity and aversion in very young children: development of a procedure

    NARCIS (Netherlands)

    Visser, J.; Kroeze, J.H.A.; Kamps, W.A.; Bijleveld, C.M.A.

    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

  19. 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

  20. 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.

  1. 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...

  2. 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...

  3. What is the most sensitive measure of water maze probe test performance?

    Directory of Open Access Journals (Sweden)

    Hamid R Maei

    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.

  4. Beam test of a one-dimensional position sensitive chamber on synchrotron radiation

    CERN Document Server

    Mei, Liu; Hui-Rong, Qi; Bao-An, Zhuang; Jian, Zhang; Rong-Guang, Liu; Qi-Ming, Zhu; Qun, Ouyang; Yuan-Bo, Chen; Xiao-Shan, Jiang; Ya-Jie, Wang; Peng, Liu; Guang-Cai, Chang

    2013-01-01

    One-dimensional single-wire chamber was developed to provide high position resolution for powder diffraction experiments with synchrotron radiation. A diffraction test using the sample of SiO2 has been accomplished at 1W2B laboratory of Beijing Synchrotron Radiation Source. The data of beam test were analyzed and some diffraction angles were obtained. The experimental results were in good agreement with standard data from ICDD powder diffraction file. The precision of diffraction angles was 1% to 4.7%. Most of relative errors between measured values of diffraction angles and existing data were less than 1%. As for the detector, the best position resolution in the test was 138 um (sigma value) with an X-ray tube. Finally, discussions of the results were given. The major factor that affected the precision of measurement was deviation from the flat structure of detector. The effect was analyzed and it came to a conclusion that it would be the optimal measurement scheme when the distance between the powder sample...

  5. Evaluation of global rainfall Measurement for Hydrological Applications in West Africa : sensitivity tests in Benin

    Science.gov (United States)

    Viarre, J.; Gosset, M.; Peugeot, C.

    2011-12-01

    We carried out an evaluation of currently available -real time or post-calibrated- rainfall products in West Africa. The work is oriented towards highlighting their skills and relevance from the view point of a hydrological end-user. The study is based on the densily instrumented meso-scale basins from the AMMA-CATCH hydrometeorological observing system. On these sites long term observations of the various term of the continental water budget and hydrological processes studies have been carried out for more than a decade. We focus here on the upper Oueme basin site in Benin (Sudanese climate - 1200 mm annual rainfall). A distributed hydrological model, developed in this framework is used to illustrate the effects of satellite based rainfall errors or uncertainty on the simulated outflow. Non linearities cause the rainfall bias to be enhanced through propagation in the model, leading to strong biases in the outflow. In addition to the biases the model response is very sensitive to the distortion in the rainfall intensities probability distribution, that some rainfall products exhibit. The AMMA-CATCH densified gages networks and hydrometeorological measurements will be integrated in the MeghaTropiques ground validation plan and used to asses the quality of MT products at the one degree one daily scale and below.

  6. 2D-Raman-THz spectroscopy: A sensitive test of polarizable water models

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, Peter, E-mail: peter.hamm@chem.uzh.ch [Department of Chemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zürich (Switzerland)

    2014-11-14

    In a recent paper, the experimental 2D-Raman-THz response of liquid water at ambient conditions has been presented [J. Savolainen, S. Ahmed, and P. Hamm, Proc. Natl. Acad. Sci. U. S. A. 110, 20402 (2013)]. Here, all-atom molecular dynamics simulations are performed with the goal to reproduce the experimental results. To that end, the molecular response functions are calculated in a first step, and are then convoluted with the laser pulses in order to enable a direct comparison with the experimental results. The molecular dynamics simulation are performed with several different water models: TIP4P/2005, SWM4-NDP, and TL4P. As polarizability is essential to describe the 2D-Raman-THz response, the TIP4P/2005 water molecules are amended with either an isotropic or a anisotropic polarizability a posteriori after the molecular dynamics simulation. In contrast, SWM4-NDP and TL4P are intrinsically polarizable, and hence the 2D-Raman-THz response can be calculated in a self-consistent way, using the same force field as during the molecular dynamics simulation. It is found that the 2D-Raman-THz response depends extremely sensitively on details of the water model, and in particular on details of the description of polarizability. Despite the limited time resolution of the experiment, it could easily distinguish between various water models. Albeit not perfect, the overall best agreement with the experimental data is obtained for the TL4P water model.

  7. Center-of-mass motion as a sensitive convergence test for variational multimode quantum dynamics

    Science.gov (United States)

    Cosme, Jayson G.; Weiss, Christoph; Brand, Joachim

    2016-10-01

    Multimode expansions in computational quantum dynamics promise convergence toward exact results upon increasing the number of modes. Convergence is difficult to ascertain in practice due to the unfavorable scaling of required resources for many-particle problems and therefore a simplified criterion based on a threshold value for the least occupied mode function is often used. Here we show how the separable quantum motion of the center of mass can be used to sensitively detect unconverged numerical multiparticle dynamics in harmonic potentials. Based on an experimentally relevant example of attractively interacting bosons in one dimension, we demonstrate that the simplified convergence criterion fails to assure qualitatively correct results. Furthermore, the numerical evidence for the creation of two-hump fragmented bright soliton-like states presented by A. I. Streltsov et al. [Phys. Rev. Lett. 100, 130401 (2008), 10.1103/PhysRevLett.100.130401] is shown to be inconsistent with exact results. Implications for understanding dynamical fragmentation in attractive boson systems are briefly discussed.

  8. A simultaneous multiple species acute toxicity test comparing relative sensitivities of six aquatic organisms to HgCl{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    McCrary, J.E.; Heagler, M.G. [McNeese State Univ., Lake Charles, LA (United States). Dept. of Biological and Environmental Science

    1995-12-31

    In the last few years there has been concern in the scientific community about observed declines in some amphibian species. These population declines could be reflecting a global phenomenon due to a general class sensitivity or may be part of a natural cycle. The suggestion of an overall greater sensitivity of amphibians is not supported. Studies show that amphibians, as a class, are neither more or less susceptible than fish to environmental conditions. Mercury has been found to be one of the most toxic of the heavy metals introduced into amphibian breeding waters. Six aquatic species were simultaneously exposed in a comparative acute toxicity test with mercury chloride: three amphibians, Rana catesbeiana (bullfrog), R. clamitans (green frog), and R. sphenocephala (southern leopard frog, formally classified as R. utricularia); two fish, Gambusia affinis (mosquitofish) and Notemigonus crysoleucas (golden shiner); one aquatic aligochaete, Lumbriculus variegatus (aquatic earthworm). The five test concentrations used were 1.4, 3.9, 12.0, 110.0, and 487.0 {micro}g Hg/L respectively. Ten organisms per species were randomly placed into the six test tanks (control and five concentrations), each species in a separate chamber. The resultant LC50-96hr values produced the following rank order: R. sphenocephala, 6.59 {micro}g Hg/L; R. clamitans, 14.7 {micro}g Hg/L; N. crysoleucas, 16.75 {micro}g Hg/L; L. variegatus, 43.72,ug Hg/L; G. affinis, 52.62 {micro}g Hg/L; R. catesbeiana, 63.36 {micro}g Hg/L. No general organism class sensitivity trend, for amphibians, was developed from this data, contrary to the implicit suggestions of some researchers.

  9. AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment.

    Science.gov (United States)

    Roach, Emma B; Bleiberg, Joseph; Lathan, Corinna E; Wolpert, Lawrence; Tsao, Jack W; Roach, Robert C

    2014-04-01

    Humans experiencing hypoxic conditions exhibit multiple signs of cognitive impairment, and high altitude expeditions may be undermined by abrupt degradation in mental performance. Therefore, the development of psychometric tools to quickly and accurately assess cognitive impairment is of great importance in aiding medical decision-making in the field, particularly in situations where symptoms may not be readily recognized. The present study used the Defense Automated Neurobehavioral Assessment (DANA), a ruggedized and portable neurocognitive assessment tool, to examine cognitive function in healthy human volunteers at sea level, immediately after ascending to an elevation over 5000 m, and following 16 days of acclimatization to this high altitude. The DANA battery begins with a simple reaction time test (SRT1) which is followed by a 20-min series of complex cognitive tests and ends with a second test of simple reaction time (SRT2). Tabulating the performance scores from these two tests allows the calculation of an SRT change score (dSRT=SRT1 - SRT2) that reflects the potential effect of mental effort spent during the 20-min testing session. We found that dSRT, but not direct SRT in comparison to sea-level baseline performance, is highly sensitive to acute altitude-related performance deficits and the remission of impairment following successful acclimatization. Our results suggest that dSRT is a potentially useful analytical method to enhance the sensitivity of neurocognitive assessment.This is an open access article distributed under the Creative Commons Attribution- Non Commercial License, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. PMID:24722229

  10. 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.

  11. 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.

  12. Testing the limits of rational design by engineering pH sensitivity into membrane active peptides

    Science.gov (United States)

    Wiedman, Gregory

    2015-01-01

    In this work, we sought to rationally design membrane active peptides that are triggered by low pH to form macromolecular-sized pores in lipid bilayers. Such peptides could have broad utility in biotechnology and in nanomedicine as cancer therapeutics or drug delivery vehicles that promote release of macromolecules from endosomes. Our approach to rational design was to combine the properties of a pH-independent peptide, MelP5, which forms large pores allowing passage of macromolecules, with the properties of two pH-dependent membrane active peptides, pHlip and GALA. We created two hybrid sequences, MelP5_Δ4 and MelP5_Δ6 by using the distribution of acidic residues on pHlip and GALA as a guide to insert acidic amino acids into the amphipathic helix of MelP5. We show that the new peptides bind to lipid bilayers and acquire secondary structure in a pH-dependent manner. The peptides also destabilize bilayers in a pH-dependent manner, such that lipid vesicles release the small molecules ANTS/DPX at low pH only. Thus, we were successful in designing pH-triggered pore-forming peptides. However, no macro-molecular release was observed under any conditions. Therefore, we abolished the unique macromolecular poration properties of MelP5 by introducing pH-sensitivity into its sequence. We conclude that the properties of pHlip, GALA and MelP5 are additive, but only partially so. We propose that this lack of additivity is a limitation in the rational design of novel membrane active peptides, and that high-throughput approaches to discovery will be critical for continued progress in the field. PMID:25572997

  13. 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.

  14. Structural dynamics modification for derrick of deep well drilling rig based on experimental modal test and frequency sensitivity analysis

    Directory of Open Access Journals (Sweden)

    Hua Jian

    2015-09-01

    Full Text Available A statically designed derrick of deep oil well drilling rig may have poor dynamic characteristics, which can cause earlier structure failure of the drilling rig and harsh working condition. One such designed derrick is found to vibrate severely in operation while the rotation speed of rotary table is about 120 r/min with the working frequency of 2.0 Hz. To solve this problem, an experimental modal test of the derrick is conducted and the modal frequencies and vibration shapes are obtained. Through comparison of modal frequencies with that of exciting devices, it is found that the severe vibration of the drilling rig is caused by the resonance of second modal frequency (1.96 Hz and the working frequency of rotary table. Based on principles of sensitivity analysis and structural dynamics modification method, the frequency sensitivities of all nodes on the derrick are calculated and compared, and then seven nodes with high-frequency sensitivity are selected on which corresponding mass are added to vary the modal frequency. Result shows that the second modal frequency of the derrick is reduced to 1.42 Hz and is out of the normal working frequency range of rotary table, which demonstrates that the dynamic characteristics of the derrick is improved and severe vibration can be avoided.

  15. 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

  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. 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.

  18. 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.

  19. Tritium labelling and characterization of the antimalarial drug (+/-)-chloroquine by several methods

    Energy Technology Data Exchange (ETDEWEB)

    Egan, J.A.Judith A.; Laseter, Anne G.; Filer, C.N.Crist N. E-mail: crist.filer@perkinelmer.com

    2002-09-01

    To study its mechanism of antimalarial action, a tritium labelled analogue of (+/-)-chloroquine was required at high specific activity. Two synthetic methods were successfully employed. [3-{sup 3}H] (+/-)-Chloroquine 2 was prepared by the catalytic tritium dehalogenation of an iodo precursor and [N-ethyl-{sup 3}H] (+/-)-chloroquine 4 was synthesized by the alkylation of (+/-)-desethylchloroquine with [{sup 3}H] ethyl iodide.

  20. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    NARCIS (Netherlands)

    Baragana, B.; Hallyburton, I.; Lee, M.C.; Norcross, N.R.; Grimaldi, R.; Otto, T.D.; Proto, W.R.; Blagborough, A.M.; Meister, S.; Wirjanata, G.; Ruecker, A.; Upton, L.M.; Abraham, T.S.; Almeida, M.J.; Pradhan, A.; Porzelle, A.; Martinez, M.S.; Bolscher, J.M.; Woodland, A.; Norval, S.; Zuccotto, F.; Thomas, J.; Simeons, F.; Stojanovski, L.; Osuna-Cabello, M.; Brock, P.M.; Churcher, T.S.; Sala, K.A.; Zakutansky, S.E.; Jimenez-Diaz, M.B.; Sanz, L.M.; Riley, J.; Basak, R.; Campbell, M.; Avery, V.M.; Sauerwein, R.W.; Dechering, K.J.; Noviyanti, R.; Campo, B.; Frearson, J.A.; Angulo-Barturen, I.; Ferrer-Bazaga, S.; Gamo, F.J.; Wyatt, P.G.; Leroy, D.; Siegl, P.; Delves, M.J.; Kyle, D.E.; Wittlin, S.; Marfurt, J.; Price, R.N.; Sinden, R.E.; Winzeler, E.A.; Charman, S.A.; Bebrevska, L.; Gray, D.W.; Campbell, S.; Fairlamb, A.H.; Willis, P.A.; Rayner, J.C.; Fidock, D.A.; Read, K.D.; Gilbert, I.H.

    2015-01-01

    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 activ

  1. Oxidative pentose phosphate pathway inhibition is a key determinant of antimalarial induced cancer cell death.

    Science.gov (United States)

    Salas, E; Roy, S; Marsh, T; Rubin, B; Debnath, J

    2016-06-01

    Despite immense interest in using antimalarials as autophagy inhibitors to treat cancer, it remains unclear whether these agents act predominantly via autophagy inhibition or whether other pathways direct their anti-cancer properties. By comparing the treatment effects of the antimalarials chloroquine (CQ) and quinacrine (Q) on KRAS mutant lung cancer cells, we demonstrate that inhibition of the oxidative arm of the pentose phosphate pathway (oxPPP) is required for antimalarial induced apoptosis. Despite inhibiting autophagy, neither CQ treatment nor RNAi against autophagy regulators (ATGs) promote cell death. In contrast, Q triggers high levels of apoptosis, both in vitro and in vivo, and this phenotype requires both autophagy inhibition and p53-dependent inhibition of the oxPPP. Simultaneous genetic targeting of the oxPPP and autophagy is sufficient to trigger apoptosis in lung cancer cells, including cells lacking p53. Thus, in addition to reduced autophagy, oxPPP inhibition serves as an important determinant of antimalarial cytotoxicity in cancer cells.

  2. 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.

  3. Detecting the antimalarial artemisinin in plant extracts using near-infrared spectroscopy

    Science.gov (United States)

    The antimalarial artemisinin is produced by Artemisia annua L and can be used to kill the protozoan parasite Plasmodium, which is spread by mosquitoes. Artemisinin is extracted from these plants through tea preparation. The artemisinin content of the tea varies depending on how much artemisinin was ...

  4. Fixed dose combination of arterolane and piperaquine: a newer prospect in antimalarial therapy.

    Science.gov (United States)

    Patil, Cy; Katare, Ss; Baig, Ms; Doifode, Sm

    2014-07-01

    Malaria has been very prevalent vector-borne disease in India and until date bears enormous implications on health care services of the country. Over the period of time, the development of resistance to traditional antimalarials like chloroquine has been posed as major deterrent in efforts of malaria control. As the drug resistance is today universally prevalent, especially in Plasmodium falciparum species, major burden of malarial control resides with the new artemisinin drug class. However, arterolane is one of the first fully synthetic non-artemisinin antimalarial compound with rapid schizontocidal activity, hence offering an alternative to artemisinin drugs in malaria control. Piperaquine is a synthetic bisquinoline (4-amioquinoline Antimalarial) with slow and longer schizontocidal activity. Therefore their combination has been shown to provide rapid parasitemic clearance and quick relief of most malaria-related symptoms along with prevention of recrudescences. This combination was approved by Drugs Controller General of India in 2011 for treatment of uncomplicated P. falciparum malaria. The article is aimed at to review this newer prospect in antimalarial therapy for which comprehensive database search was done in Google, Google Scholar, PubMed using the terms "Malaria," "Arterolane," "OZ277," "Piperaquine," and "Artemisinin combination therapy." A total of 323 articles were screened and 28 articles were considered for this review along with the World Health Organization and National malarial program guidelines.

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Comparison of the sensitivity of Danio rerio and Poecilia reticulata to silver nitrate in short-term tests.

    Science.gov (United States)

    Doleželová, Petra; Mácová, Stanislava; Pištěková, Vladimíra; Svobodová, Zdeňka; Bedáňová, Iveta; Voslářová, Eva

    2008-09-01

    The aim of this study is to assess the acute toxicity of silver nitrate in adult zebra fish and adult guppies and to compare the sensitivity of these species to this compound. Silver is a naturally occurring element in our environment and it combines with other elements such as sulfide, chloride, and nitrate. Silver, in the form of silver nitrate, is one of the most toxic metals affecting freshwater fish. Industry, particularly photographical and electrotechnical, is the major contributor of silver that is released into the environment. Tests of acute toxicity were performed on the most common species of aquarium fish, Danio rerio and Poecilia reticulata. Both zebra fish and guppies were exposed to progressive concentrations of silver nitrate; a semi-static method according to OECD 203 was used. In each test series, 6 tests of acute toxicity were conducted, with 10 fish used for each separate concentration and for the control group. The results (number of fish deaths in the individual test concentrations) were subjected to probit analysis (EKO-TOX 5.1 software) to determine the 96hLC(50) AgNO(3) values. The 96hLC(50) AgNO(3) value for the zebra fish was (mean±SEM) 15±0.52 µg/l and for the guppies was (mean±SEM) 17.14±5.43 µg/l. We didn't find any statistically significant difference between the sensitivity of zebra fish and guppies. The results reported in this study are in agreement with LC(50) values published in peer-reviewed literature, and conclude that AgNO(3) is one of the most toxic compounds known to fishery. PMID:21218114

  13. 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.

  14. The Changes of Baroreflex Sensitivity During Head -up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

    Institute of Scientific and Technical Information of China (English)

    胡兆霆; 吕艳青; 杨钧国

    2001-01-01

    Objective To study the changes of baroreflex sensitivity (BRS) during head -up tilt test (HUT) in patients with vasovagal syncope (VS),and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS.Methods Forty- two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head-up tilt testing, Antecubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin ,serum nitric oxide (NO), serum NE were measured. The BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results ( 1 )During the syncope, the BRS significantly reduced in HUT( + ) group than baseline. At the end of tilt, the level of plasma ET, serum NO in patients with positive HUT significantly increased compared with baseline or normal controls, and the plasma concentration of NE also had the trend of increase. ( 2 ) By multiple regression analysis, a significant negative correlation was found between baroreceptor sensitivity and the plasma ET, NO at the end of HUT in patients with positive HUT, but there was no relationship between BRS and NE. Conclusions During the syncope occure, the BRS in patients with VS decreased significantly compared with normal controls. The abnormal plasma ET, NO concentration might contribute to the mechanism of VS.

  15. 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 ; ...

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. Effects of test media on reproduction in Potamopyrgus antipodarum and of pre-exposure population densities on sensitivity to cadmium in a reproduction test.

    Science.gov (United States)

    Sieratowicz, Agnes; Schulte-Oehlmann, Ulrike; Wigh, Adriana; Oehlmann, Jörg

    2013-01-01

    Molluscan species can be affected by various anthropogenic substances. Yet, these effects are disregarded in chemical risk assessment as molluscs are unrepresented in standard OECD guidelines. The project "validation of a mollusc reproduction test" (Federal Environment Agency, code 371165417) deals with the development of a test method with the mudsnail Potamopyrgus antipodarum for OECD purposes. In this context, the influence on reproduction of both, different media and varying snail density, has been observed in independent experiments. Further, the impact of density on the outcome of subsequent cadmium (Cd) toxicity in a test has been investigated to refine the existing methodology. First, adult snails were kept in different test media for 12 weeks. Second, snail density was increased for 4 weeks to induce stress. Snails from each density scenario were used for another 4 weeks in a reproduction test at an equal density with 12 μg Cd/L, respectively. Significant differences in reproduction between medium groups were noted after 4 and 8, but not 12, weeks. Further, reproduction was significantly altered by snail density in the beakers but after subsequent 4 weeks at a constant density, no differences were observed between control groups. Cd reduced reproduction and this effect increased with snail density in the pre-exposure period, demonstrating that a previous stress factor may result in increased sensitivity to chemicals and underlines the need for more standardized breeding conditions to minimize effect variations. Based on the outcome of this study, an acclimatization period of 12 weeks must be guaranteed for specimens transferred to another medium. Further, 4 weeks of acclimatization are necessary after density stress. An additional 12 weeks density experiment showed that medium volume in each replicate can be decreased by half to save on chemicals, water and space during tests.

  2. 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.

  3. 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

  4. 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)

  5. 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.

  6. 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

  7. 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 ...

  8. 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...

  9. 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...

  10. Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings.

    Directory of Open Access Journals (Sweden)

    Stefanie Knopp

    2015-05-01

    Full Text Available Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025. Conventional parasitological methods are insensitive for the detection of light-intensity infections. Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings and verification of elimination. We determined the accuracy of a urine-based up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA assay for Schistosoma haematobium diagnosis in low-prevalence settings in Zanzibar, Tanzania.A total of 1,740 urine samples were collected in 2013 from children on Pemba Island, from schools where the S. haematobium prevalence was <2%, 2-5%, and 5-10%, based on a single urine filtration. On the day of collection, all samples were tested for microhematuria with reagent strips and for the presence of S. haematobium eggs with microscopy. Eight months later, 1.5 ml of urine from each of 1,200 samples stored at -20°C were analyzed by UCP-LF CAA assay, while urine filtration slides were subjected to quality control (QCUF. In the absence of a true 'gold' standard, the diagnostic performance was calculated using latent class analyses (LCA.The 'empirical' S. haematobium prevalence revealed by UCP-LF CAA, QCUF, and reagent strips was 14%, 5%, and 4%, respectively. LCA revealed a sensitivity of the UCP-LF CAA, QCUF, and reagent strips of 97% (95% confidence interval (CI: 91-100%, 86% (95% CI: 72-99%, and 67% (95% CI: 52-81%, respectively. Test specificities were consistently above 90%.The UCP-LF CAA assay shows high sensitivity for the diagnosis of S. haematobium in low-endemicity settings. Empirically, it detects a considerably higher number of infections than microscopy. Hence, the UCP-LF CAA employed in combination with QCUF, is a promising tool for monitoring and surveillance of urogenital schistosomiasis in low

  11. 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.

  12. 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

  13. Nitrogen-14 nuclear quadrupole resonance spectroscopy: a promising analytical methodology for medicines authentication and counterfeit antimalarial analysis.

    Science.gov (United States)

    Barras, Jamie; Murnane, Darragh; Althoefer, Kaspar; Assi, Sulaf; Rowe, Michael D; Poplett, Iain J F; Kyriakidou, Georgia; Smith, John A S

    2013-03-01

    We report the detection and analysis of a suspected counterfeit sample of the antimalarial medicine Metakelfin through developing nitrogen-14 nuclear quadrupole resonance ((14)N NQR) spectroscopy at a quantitative level. The sensitivity of quadrupolar parameters to the solid-state chemical environment of the molecule enables development of a technique capable of discrimination between the same pharmaceutical preparations made by different manufacturers. The (14)N NQR signal returned by a tablet (or tablets) from a Metakelfin batch suspected to be counterfeit was compared with that acquired from a tablet(s) from a known-to-be-genuine batch from the same named manufacturer. Metakelfin contains two active pharmaceutical ingredients, sulfalene and pyrimethamine, and NQR analysis revealed spectral differences for the sulfalene component indicative of differences in the processing history of the two batches. Furthermore, the NQR analysis provided quantitative information that the suspected counterfeit tablets contained only 43 ± 3%, as much sulfalene as the genuine Metakelfin tablets. Conversely, conventional nondestructive analysis by Fourier transform (FT)-Raman and FT-near infrared (NIR) spectroscopies only achieved differentiation between batches but no ascription. High performance liquid chromatography (HPLC)-UV analysis of the suspect tablets revealed a sulfalene content of 42 ± 2% of the labeled claim. The degree of agreement shows the promise of NQR as a means of the nondestructive identification and content-indicating first-stage analysis of counterfeit pharmaceuticals.

  14. 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.

  15. Sensitivity and Specificity of a New Vertical Flow Rapid Diagnostic Test for the Serodiagnosis of Human Leptospirosis.

    Directory of Open Access Journals (Sweden)

    Cyrille Goarant

    2013-06-01

    Full Text Available Background : Leptospirosis is a growing public health concern in many tropical and subtropical countries. However, its diagnosis is difficult because of non-specific symptoms and concurrent other endemic febrile diseases. In many regions, the laboratory diagnosis is not available due to a lack of preparedness and simple diagnostic assay or difficult access to reference laboratories. Yet, an early antibiotic treatment is decisive to the outcome. The need for Rapid Diagnostic Tests (RDTs for bedside diagnosis of leptospirosis has been recognized. We developed a vertical flow immunochromatography strip RDT detecting anti-Leptospira human IgM and evaluated it in patients from New Caledonia, France, and French West Indies. Methodology/Principal Findings : Whole killed Leptospira fainei cells were used as antigen for the test line and purified human IgM as the control line. The mobile phase was made of gold particles conjugated with goat anti-human IgM. Standards for Reporting of Diagnostic Accuracy criteria were used to assess the performance of this RDT. The Microscopic Agglutination Test (MAT was used as the gold standard with a cut-off titer of ≥400. The sensitivity was 89.8% and the specificity 93.7%. Positive and negative Likelihood Ratios of 14.18 and 0.108 respectively, and a Diagnostic Odds Ratio of 130.737 confirmed its usefulness. This RDT had satisfactory reproducibility, repeatability, thermal tolerance and shelf-life. The comparison with MAT evidenced the earliness of the RDT to detect seroconversion. When compared with other RDT, the Vertical Flow RDT developed displayed good diagnostic performances.This RDT might be used as a point of care diagnostic tool in limited resources countries. An evaluation in field conditions and in other epidemiological contexts should be considered to assess its validity over a wider range of serogroups or when facing different endemic pathogens. It might prove useful in endemic contexts or outbreak

  16. Novel Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model*

    OpenAIRE

    Booker, Michael L.; Bastos, Cecilia M.; Kramer, Martin L.; Barker, 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

    2010-01-01

    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 ...

  17. ANTIMALARIAL DRUGS IN THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS: PAST, PRESENT, FUTURE

    Directory of Open Access Journals (Sweden)

    Tatyana Andreyevna Lisitsyna

    2010-01-01

    Full Text Available The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed

  18. Preliminary assessment of medicinal plants used as antimalarials in the southeastern Venezuelan Amazon

    Directory of Open Access Journals (Sweden)

    Caraballo Alejandro

    2004-01-01

    Full Text Available Eighteen species of medicinal plants used in the treatment of malaria in Bolívar State, Venezuela were recorded and they belonged to Compositae, Meliaceae, Anacardiaceae, Bixaceae, Boraginaceae, Caricaceae, Cucurbitaceae, Euphorbiaceae, Leguminosae, Myrtaceae, Phytolaccaceae, Plantaginaceae, Scrophulariaceae, Solanaceae and Verbenaceae families. Antimalarial plant activities have been linked to a range of compounds including anthroquinones, berberine, flavonoids, limonoids, naphthquinones, sesquiterpenes, quassinoids, indol and quinoline alkaloids.

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

    OpenAIRE

    Bertocchi Paola; Antoniella Eleonora; Cocchieri Emilia; Di Maggio Anna; Gaudiano Maria; Alimonti Stefano; Valvo Luisa

    2007-01-01

    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 ...

  20. Antimalarial Chemotherapy: Natural Product Inspired Development of Preclinical and Clinical Candidates with Diverse Mechanisms of Action.

    Science.gov (United States)

    Fernández-Álvaro, Elena; Hong, W David; Nixon, Gemma L; O'Neill, Paul M; Calderón, Félix

    2016-06-23

    Natural products have played a pivotal role in malaria chemotherapy progressing from quinine and artemisinin to ozonide-based compounds. Many of these natural products have served as template for the design and development of antimalarial drugs currently in the clinic or in the development phase. In this review, we will detail those privileged scaffolds that have guided medicinal chemistry efforts yielding molecules that have reached the clinic. PMID:26791529