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chloroquine resistance

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https://www.readbyqxmd.com/read/28931241/association-of-a-novel-mutation-in-the-plasmodium-falciparum-chloroquine-resistance-transporter-with-decreased-piperaquine-sensitivity
#1
Sonia Agrawal, Kara A Moser, Lindsay Morton, Michael P Cummings, Ankita Parihar, Ankit Dwivedi, Amol C Shetty, Elliott F Drabek, Christopher G Jacob, Philipp P Henrich, Christian M Parobek, Krisada Jongsakul, Rekol Huy, Michele D Spring, Charlotte A Lanteri, Suwanna Chaorattanakawee, Chanthap Lon, Mark M Fukuda, David L Saunders, David A Fidock, Jessica T Lin, Jonathan J Juliano, Christopher V Plowe, Joana C Silva, Shannon Takala-Harrison
Background: Amplified copy number in the plasmepsin II/III genes within Plasmodium falciparum has been associated with decreased sensitivity to piperaquine. To examine this association and test whether additional loci might also contribute, we performed a genome-wide association study of ex vivo P. falciparum susceptibility to piperaquine. Methods: Plasmodium falciparum DNA from 183 samples collected primarily from Cambodia was genotyped at 33716 genome-wide single nucleotide polymorphisms (SNPs)...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28923866/changing-antimalarial-drug-sensitivities-in-uganda
#2
Stephanie A Rasmussen, Frida G Ceja, Melissa D Conrad, Patrick K Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Samuel L Nsobya, Philip J Rosenthal, Roland A Cooper
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28917086/kostchyienones-a-and-b-new-antiplasmodial-and-cytotoxicity-of-limonoids-from-the-roots-of-pseudocedrela-kotschyi-schweinf-harms
#3
Lazare S Sidjui, Yves O D Nganso, Rufin M K Toghueo, Brussine N K Wakeu, Joel T Dameue, Pierre Mkounga, Achyut Adhikari, Mehreen Lateef, Gabriel N Folefoc, Muhammad S Ali
Two new limonoids, kostchyienones A (1) and B (2), along with 12 known compounds 3-14 were isolated from the roots of Pseudocedrela kostchyi. Compound (7) was isolated for the first time from a natural source. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1-6 and 13-14 gave IC50 values ranging from 0.75 to 5.62 μg/mL for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compound 5 showed moderate potential cytotoxicity against the HEK239T cell line with an IC50 value of 22...
September 16, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28916443/aq-13-an-investigational-antimalarial-versus-artemether-plus-lumefantrine-for-the-treatment-of-uncomplicated-plasmodium-falciparum-malaria-a-randomised-phase-2-non-inferiority-clinical-trial
#4
Ousmane A Koita, Lansana Sangaré, Haiyan D Miller, Aliou Sissako, Moctar Coulibaly, Trevor A Thompson, Saharé Fongoro, Youssouf Diarra, Mamadou Ba, Ababacar Maiga, Boubakar Diallo, David M Mushatt, Frances J Mather, Jeffrey G Shaffer, Asif H Anwar, Donald J Krogstad
BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood)...
September 12, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28913784/managing-wastes-as-green-resources-cigarette-butt-synthesized-pesticides-are-highly-toxic-to-malaria-vectors-with-little-impact-on-predatory-copepods
#5
Kadarkarai Murugan, Udaiyan Suresh, Chellasamy Panneerselvam, Rajapandian Rajaganesh, Mathath Roni, Al Thabiani Aziz, Jiang-Shiou Hwang, Kuppusamy Sathishkumar, Aruliah Rajasekar, Suresh Kumar, Abdullah A Alarfaj, Akon Higuchi, Giovanni Benelli
The development of novel mosquito control tools is a key prerequisite to build effective and reliable Integrated Vector Management strategies. Here, we proposed a novel method using cigarette butts for the synthesis of Ag nanostructures toxic to young instars of the malaria vector Anopheles stephensi, chloroquine (CQ)-resistant malaria parasites Plasmodium falciparum and microbial pathogens. The non-target impact of these nanomaterials in the aquatic environment was evaluated testing them at sub-lethal doses on the predatory copepod Mesocyclops aspericornis...
September 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28903368/expression-analysis-of-lc3b-and-p62-indicates-intact-activated-autophagy-is-associated-with-an-unfavorable-prognosis-in-colon-cancer
#6
Monique Niklaus, Olivia Adams, Sabina Berezowska, Inti Zlobec, Franziska Graber, Julia Slotta-Huspenina, Ulrich Nitsche, Robert Rosenberg, Mario P Tschan, Rupert Langer
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. We assessed the impact of basal autophagy in colon cancer (CC) in vitro and ex vivo. Functional autophagy was demonstrated in CC cell lines (LoVo; HT-29) showing a dose-dependent increase of the autophagy markers LC3B, p62 and autophagic vesciles upon increasing concentrations of the autophagy inhibitor chloroquine, which was demonstrated by immunoblotting, immunofluorescence and electron microscopy...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898049/analysis-of-plasmodium-vivax-chloroquine-resistance-transporter-pvcrt-mutant-isoforms
#7
Matthew R Hassett, Bryce E Riegel, Paul Samuel Callaghan, Paul David Roepe
Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum malaria is widespread and has limited the use of CQ in many regions of the globe. Malaria caused by the related human parasite P. vivax is as widespread as is P. falciparum malaria and has been treated with CQ as extensively as has P. falciparum, suggesting that P. vivax parasites have been selected with CQ as profoundly as have P. falciparum parasites. Indeed, a growing number of clinical reports have presented data suggesting increased P. vivax CQR...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28893216/antimalarial-efficacy-of-pongamia-pinnata-l-pierre-against-plasmodium-falciparum-3d7-strain-and-plasmodium-berghei-anka
#8
P V V Satish, K Sunita
BACKGROUND: The objective of the current study was to assess the in vitro antiplasmodial activities of leaf, bark, flower, and the root of Pongamia pinnata against chloroquine-sensitive Plasmodium falciparum (3D7 strain), cytotoxicity against Brine shrimp larvae and THP-1 cell line. For in vivo study, the plant extract which has shown potent in vitro antimalarial activity was tested against Plasmodium berghei (ANKA strain). METHODS: The plant Pongamia pinnata was collected from the herbal garden of Acharya Nagarjuna University of Guntur district, Andhra Pradesh, India...
September 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28887215/antiprotozoal-activity-of-medicinal-plants-used-by-iquitos-nauta-road-communities-in-loreto-peru
#9
Pedro Vásquez-Ocmín, Sandrine Cojean, Elsa Rengifo, Soulaf Suyyagh-Albouz, Carlos A Amasifuen Guerra, Sébastien Pomel, Billy Cabanillas, Kember Mejía, Philippe M Loiseau, Bruno Figadère, Alexandre Maciuk
ETHNOPHARMACOLOGICAL RELEVANCE: In the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies...
September 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28886443/antiplasmodial-activities-of-dyes-against-plasmodium-falciparum-asexual-and-sexual-stages-contrasted-uptakes-of-triarylmethanes-brilliant-green-green-s-e142-and-patent-blue-v-e131-by-erythrocytes
#10
Louis-Jérôme Leba, Jean Popovici, Yannick Estevez, Stéphane Pelleau, Eric Legrand, Lise Musset, Christophe Duplais
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P...
August 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28882160/intrinsic-fluorescence-of-the-clinically-approved-multikinase-inhibitor-nintedanib-reveals-lysosomal-sequestration-as-resistance-mechanism-in-fgfr-driven-lung-cancer
#11
Bernhard Englinger, Sebastian Kallus, Julia Senkiv, Daniela Heilos, Lisa Gabler, Sushilla van Schoonhoven, Alessio Terenzi, Patrick Moser, Christine Pirker, Gerald Timelthaler, Walter Jäger, Christian R Kowol, Petra Heffeter, Michael Grusch, Walter Berger
BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28881678/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#12
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875471/optimization-of-curcuma-oil-quinine-loaded-nanocapsules-for-malaria-treatment
#13
Graziela Scheuer Gomes, Tamara Ramos Maciel, Eduarda Martini Piegas, Luana Roberta Michels, Letícia Marques Colomé, Rodrigo José Freddo, Daiana Silva de Ávila, Andre Gundel, Sandra Elisa Haas
Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit(®) RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 2(4) factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice...
September 5, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28874885/ethanol-extract-of-blighia-sapida-stem-bark-show-remarkable-prophylactic-activity-in-experimental-plasmodium-berghei-infected-mice
#14
Olayinka O Otegbade, Johnson A Ojo, Dolapo I Adefokun, Oyindamola O Abiodun, Bolaji N Thomas, Olusola Ojurongbe
This work explores the antiplasmodial potential of ethanol extract of Blighia sapida (Lin. Sapindaceae) in chloroquine (CQ)-resistant Plasmodium berghei (ANKA strain)-infected mice. Chloroquine-resistant (ANKA) strain of P berghei was inoculated intraperitoneally into Swiss albino mice. Mice were treated orally for 4 consecutive days, before and after inoculation (prophylactic, suppressive, and curative models) with graded doses of the plant extracts with Artemether-Lumefantrine (Coartem) as control. Prophylactically, the extract showed a remarkable activity in the chemosuppression of P berghei parasites (P < ...
2017: Drug Target Insights
https://www.readbyqxmd.com/read/28860870/early-treatment-failure-in-concurrent-dengue-and-mixed-malaria-species-infection-with-suspected-resistance-to-artemisinin-combination-therapy-from-a-tertiary-care-center-in-delhi-a-case-report
#15
Rushika Saksena, Monika Matlani, Vineeta Singh, Amit Kumar, Anupam Anveshi, Dilip Kumar, Rajni Gaind
BACKGROUND: Concurrent dengue and mixed malaria infections in a single patient present with overlapping clinical manifestations which pose a diagnostic challenge and management dilemma in areas of common endemicities. METHODS: We report a case of a young male who tested positive for both Plasmodium vivax and Plasmodium falciparum along with dengue infection. He showed signs of early treatment failure to artemisinin combination therapy (artesunate with sulfadoxine+pyrimethamine)...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28856028/bibliometric-analysis-of-worldwide-publications-on-antimalarial-drug-resistance-2006-2015
#16
REVIEW
Waleed M Sweileh, Samah W Al-Jabi, Ansam F Sawalha, Adham S AbuTaha, Sa'ed H Zyoud
BACKGROUND: In response to international efforts to control and eradicate malaria, we designed this study to give a bibliometric overview of research productivity in antimalarial drug resistance (AMDR). METHODS: Keywords related to AMDR were used to retrieve relevant literature using Scopus database. RESULTS: A total of 976 publications with an h-index of 63 were retrieved. The number of publications showed a noticeable increase starting in the early 1990s...
2017: Malaria Research and Treatment
https://www.readbyqxmd.com/read/28839145/dact1-overexpression-in-type-i-ovarian-cancer-inhibits-malignant-expansion-and-cis-platinum-resistance-by-modulating-canonical-wnt-signalling-and-autophagy
#17
Ruo-Nan Li, Bin Liu, Xue-Mei Li, Liang-Si Hou, Xiao-Ling Mu, Hui Wang, Hua Linghu
Type I epithelial ovarian cancer (EOC) is primarily resistant to platinum-based chemotherapies and needs novel therapeutics. Given the aberrant Wnt activation in type I EOC and the involvement of Dapper1 Antagonist of Catenin-1 (DACT1) in Wnt signalling, the role of DACT1 in tumourigenesis of type I EOC was evaluated. Firstly, all tested EOC cell lines and primary EOC tissues, especially type I EOC, were observed to have significantly lower DACT1 expression than normal controls. Next, 3AO cells, which arise from a patient with primary mucinous EOC and express low endogenous levels of DACT1, were transfected with a lentivirus carrying full-length DACT1 (3AO-DACT1), grew slower and formed smaller tumours in nude mice compared to 3AO-NC...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837152/lysosomotropism-depends-on-glucose-a-chloroquine-resistance-mechanism
#18
Laura E Gallagher, Ohood A Radhi, Mahmud O Abdullah, Anthony G McCluskey, Marie Boyd, Edmond Y W Chan
There has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28837150/three-dimensional-tumor-cell-growth-stimulates-autophagic-flux-and-recapitulates-chemotherapy-resistance
#19
Corinna Bingel, Emily Koeneke, Johannes Ridinger, Annika Bittmann, Martin Sill, Heike Peterziel, Jagoda K Wrobel, Inga Rettig, Till Milde, Uta Fernekorn, Frank Weise, Andreas Schober, Olaf Witt, Ina Oehme
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28829723/sustained-high-cure-rate-of-artemether-lumefantrine-against-uncomplicated-plasmodium-falciparum-malaria-after-8-years-of-its-wide-scale-use-in-bagamoyo-district-tanzania
#20
Richard Mwaiswelo, Billy Ngasala, J Pedro Gil, Maja Malmberg, Irina Jovel, Weiping Xu, Zul Premji, Bruno P Mmbando, Anders Björkman, Andreas Mårtensson
We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation...
August 2017: American Journal of Tropical Medicine and Hygiene
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