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https://www.readbyqxmd.com/read/28320390/false-negative-malaria-rapid-diagnostic-tests-in-rwanda-impact-of-plasmodium-falciparum-isolates-lacking-hrp2-and-declining-malaria-transmission
#1
Christina T Kozycki, Noella Umulisa, Stephen Rulisa, Emil I Mwikarago, Jean Pierre Musabyimana, Jean Pierre Habimana, Corine Karema, Donald J Krogstad
BACKGROUND: Rapid diagnostic tests (RDTs) for histidine rich protein 2 (HRP2) are often used to determine whether persons with fever should be treated with anti-malarials. However, Plasmodium falciparum parasites with a deletion of the hrp2 gene yield false-negative RDTs and there are concerns the sensitivity of HRP2-based RDTs may fall when the intensity of transmission decreases. METHODS: This observational study enrolled 9226 patients at three health centres in Rwanda from April 2014 to April 2015...
March 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28292906/parasitophorous-vacuole-poration-precedes-its-rupture-and-rapid-host-erythrocyte-cytoskeleton-collapse-in-plasmodium-falciparum-egress
#2
Victoria L Hale, Jean M Watermeyer, Fiona Hackett, Gema Vizcay-Barrena, Christiaan van Ooij, James A Thomas, Matthew C Spink, Maria Harkiolaki, Elizabeth Duke, Roland A Fleck, Michael J Blackman, Helen R Saibil
In the asexual blood stages of malarial infection, merozoites invade erythrocytes and replicate within a parasitophorous vacuole to form daughter cells that eventually exit (egress) by sequential rupture of the vacuole and erythrocyte membranes. The current model is that PKG, a malarial cGMP-dependent protein kinase, triggers egress, activating malarial proteases and other effectors. Using selective inhibitors of either PKG or cysteine proteases to separately inhibit the sequential steps in membrane perforation, combined with video microscopy, electron tomography, electron energy loss spectroscopy, and soft X-ray tomography of mature intracellular Plasmodium falciparum parasites, we resolve intermediate steps in egress...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283009/-production-and-molecular-characterization-of-plasmodium-falciparum-recombinant-circumsporozoite-protein-with-37-nanp-and-4-nvdp-epitopes
#3
Yunus Uyar, Abdüssamed Akşit, Serkan Karaca, Şirin Sahra Ceylan, Merve Yürük
Malaria is caused by the protozoan parasite Plasmodium, the leading cause of death amongst the parasitic diseases. The disease is transmitted to human by the bites of female Anopheles mosquitoes. According to the World Health Organization (WHO) data, there were an estimated 214 million malaria cases and estimated 438.000 deaths occurred worldwide, in 2015. It is observed that 90% of all the deaths due to malaria occur in Africa. 78% of these cases were children who are under five years old. Intensive malaria interventions helped to reduce malaria incidence by 37% between 2000 and 2015...
January 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28270152/a-systematic-review-on-malaria-sero-epidemiology-studies-in-the-brazilian-amazon-insights-into-immunological-markers-for-exposure-and-protection
#4
Pedro M Folegatti, André M Siqueira, Wuelton M Monteiro, Marcus Vinícius G Lacerda, Chris J Drakeley, Érika M Braga
BACKGROUND: Considerable success in reducing malaria incidence and mortality has been achieved in Brazil, leading to discussions over the possibility of moving towards elimination. However, more than reporting and counting clinical cases, elimination will require the use of efficient tools and strategies for measuring transmission dynamics and detecting the infectious reservoir as the primary indicators of interest for surveillance and evaluation. Because acquisition and maintenance of anti-malarial antibodies depend on parasite exposure, seroprevalence rates could be used as a reliable tool for assessing malaria endemicity and an adjunct measure for monitoring transmission in a rapid and cost-effective manner...
March 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28258239/the-pushmi-pullyu-of-resistance-to-chloroquine-in-malaria
#5
REVIEW
Ruth Skrzypek, Richard Callaghan
Malarial infection continues to impart devastating health problems in the developing world. Treatment of malaria has involved chemotherapy since 168 BC, with the most prevalent and successful forms using plant alkaloids. Perhaps the greatest treatment success against malaria was by chloroquine, a synthetic derivative of the quinines found in the Cinchona tree bark. Chloroquine is able to kill parasites by interfering with haem metabolism in the parasite's digestive vacuole. The widespread use of chloroquine predictably resulted in the development of drug-resistant malaria and the most highly implicated resistance mediators are the transporter proteins P-glycoprotein (P-gp) homologue 1 (P-gh1) and Plasmodium falciparum chloroquine-resistance transporter (PfCRT), which reside on the parasite's digestive vacuole...
February 28, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28252130/an-embedded-barcode-for-connected-malaria-rapid-diagnostic-tests
#6
Thomas F Scherr, Sparsh Gupta, David W Wright, Frederick R Haselton
Many countries are shifting their efforts from malaria control to disease elimination. New technologies will be necessary to meet the more stringent demands of elimination campaigns, including improved quality control of malaria diagnostic tests, as well as an improved means for communicating test results among field healthcare workers, test manufacturers, and national ministries of health. In this report, we describe and evaluate an embedded barcode within standard rapid diagnostic tests as one potential solution...
March 2, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28242687/quantification-of-labile-heme-in-live-malaria-parasites-using-a-genetically-encoded-biosensor
#7
James R Abshire, Christopher J Rowlands, Suresh M Ganesan, Peter T C So, Jacquin C Niles
Heme is ubiquitous, yet relatively little is known about the maintenance of labile pools of this cofactor, which likely ensures its timely bioavailability for proper cellular function. Quantitative analysis of labile heme is of fundamental importance to understanding how nature preserves access to the diverse chemistry heme enables, while minimizing cellular damage caused by its redox activity. Here, we have developed and characterized a protein-based sensor that undergoes fluorescence quenching upon heme binding...
February 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195463/target-elucidation-by-cocrystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#8
Yiqing Yang, You Yu, Xiaolu Li, Jing Li, Yue Wu, Jie Yu, Jingpeng Ge, Zhenghui Huang, Lubin Jiang, Yu Rao, Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28188731/design-in-silico-and-in%C3%A2-vitro-evaluation-of-curcumin-analogues-against-plasmodium-falciparum
#9
Chandrajit Dohutia, Dipak Chetia, Kabita Gogoi, Kishore Sarma
The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca(2+) ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity...
February 7, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28183299/avidity-of-anti-malarial-antibodies-inversely-related-to-transmission-intensity-at-three-sites-in-uganda
#10
Isaac Ssewanyana, Emmanuel Arinaitwe, Joaniter I Nankabirwa, Adoke Yeka, Richard Sullivan, Moses R Kamya, Philip J Rosenthal, Grant Dorsey, Harriet Mayanja-Kizza, Chris Drakeley, Bryan Greenhouse, Kevin K A Tetteh
BACKGROUND: People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection...
February 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28152649/anti-inflammatory-anti-cholinergic-and-cytotoxic-effects-of-sida-rhombifolia
#11
Siau Hui Mah, Soek Sin Teh, Gwendoline Cheng Lian Ee
CONTEXT: Sida (Malvaceae) has been used as a traditional remedy for the treatment of diarrhoea, malarial, gastrointestinal dysentery, fevers, asthma and inflammation. OBJECTIVES: This study evaluates the anti-inflammatory, cytotoxic and anti-cholinergic activities of Sida rhombifolia Linn. whole plant for the first time. MATERIALS AND METHODS: S. rhombifolia whole plant was extracted by n-hexane, ethyl acetate and methanol using Soxhlet apparatus...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28146103/role-of-quinone-reductase-2-in-the-antimalarial-properties-of-indolone-type-derivatives
#12
Laure-Estelle Cassagnes, Nambinina Rakotoarivelo, Serena Sirigu, Pierre Pério, Ennaji Najahi, Léonard M G Chavas, Andrew Thompson, Régis Gayon, Gilles Ferry, Jean A Boutin, Alexis Valentin, Karine Reybier, Françoise Nepveu
Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives...
January 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28076793/chloroquine-inducible-par-4-secretion-is-essential-for-tumor-cell-apoptosis-and-inhibition-of-metastasis
#13
Ravshan Burikhanov, Nikhil Hebbar, Sunil K Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S Watt, Danny R Welch, Jodi Maranchie, Akihiro Harada, Vivek M Rangnekar
The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28036313/pretreatment-elevated-erythrocyte-sedimentation-rate-and-c-reactive-protein-as-a-predictor-of-malarial-complications
#14
Sachin Vemula, Vidyalakshmi Katara, Unnikrishnan Bhaskaran, Sushma Adappa, Mahabala Chakrapani
INTRODUCTION: Complications of malaria can develop suddenly and unexpectedly. Although various parameters have been associated with severity of malaria, they have not been studied as predictors of these events. Many of the malarial complications are inflammatory in nature, and C-reactive protein (CRP) and elevated erythrocyte sedimentation rate (ESR) could be early markers of these complications and might precede and predict the development of complications. METHODOLOGY: A total of 122 inpatients with uncomplicated newly diagnosed malaria were studied...
December 30, 2016: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/28031457/force-spectroscopy-of-the-plasmodium-falciparum-vaccine-candidate-circumsporozoite-protein-suggests-a-mechanically-pliable-repeat-region
#15
Aditya Prasad Patra, Shobhona Sharma, Sri Rama Koti Ainavarapu
The most effective vaccine candidate of malaria is based on the Plasmodium falciparum circumsporozoite protein (CSP), a major surface protein implicated in the structural strength, motility, and immune evasion properties of the infective sporozoites. It is suspected that reversible conformational changes of CSP are required for infection of the mammalian host, but the detailed structure and dynamic properties of CSP remain incompletely understood, limiting our understanding of its function in the infection...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28012440/nrf2-inhibition-reverses-the-resistance-of-cisplatin-resistant-head-and-neck-cancer-cells-to-artesunate-induced-ferroptosis
#16
Jong-Lyel Roh, Eun Hye Kim, Hyejin Jang, Daiha Shin
Artesunate, an anti-malarial drug, has been repurposed as an anticancer drug due to its induction of cell death via reactive oxygen species (ROS) production. However, the molecular mechanisms regulating cancer cell death and the resistance of cells to artesunate remain unclear. We investigated the molecular mechanisms behind the antitumor effects of artesunate and an approach to overcome artesunate resistance in head and neck cancer (HNC). The effects of artesunate and trigonelline were tested in different HNC cell lines, including three cisplatin-resistant HNC cell lines...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28000518/artemisinin-inhibits-inflammatory-response-via-regulating-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#17
Ke Si Wang, Junbo Li, Zhe Wang, Chunliu Mi, Juan Ma, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Xuejun Jin
Artemisinin, isolated from the Chinese plant Artemisia annua, has been used for many years to treat different forms of malarial parasites. In this study, we explored the anti-inflammatory activity of artemisinin and the underlying mechanism of this action. We demonstrated that the anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice. Then the artemisinin significantly inhibited the expression of NF-κB reporter gene induced by TNF-α in a dose-dependent manner. Artemisinin also inhibited TNF-α induced phosphorylation and degradation of IκBα, p65 nuclear translocation...
February 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/27941926/dihydroartemisinin-inhibits-catabolism-in-rat-chondrocytes-by-activating-autophagy-via-inhibition-of-the-nf-%C3%AE%C2%BAb-pathway
#18
Li-Bo Jiang, De-Hua Meng, Soo-Min Lee, Shu-Hao Liu, Qin-Tong Xu, Yang Wang, Jian Zhang
Osteoarthritis is a disease with inflammatory and catabolic imbalance in cartilage. Dihydroartemisinin (DHA), a natural and safe anti-malarial agent, has been reported to inhibit inflammation, but its effects on chondrocytes have yet to be elucidated. We investigated the effects of DHA on catabolism in chondrocytes. Viability of SD rats chondrocytes was analyzed. Autophagy levels were determined via expression of autophagic markers LC3 and ATG5, GFP-LC3 analysis, acridine orange staining, and electron microscopy...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27936446/design-synthesis-and-evaluation-of-4-aminoquinoline-purine-hybrids-as-potential-antiplasmodial-agents
#19
P Linga Reddy, Shabana I Khan, Prija Ponnan, Mohit Tripathi, Diwan S Rawat
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P...
January 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27923179/structural-dynamics-of-casein-kinase-i-cki-from-malarial-parasite-plasmodium-falciparum-isolate-3d7-insights-from-theoretical-modelling-and-molecular-simulations
#20
Budheswar Dehury, Santosh Kumar Behera, Namita Mahapatra
The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation...
January 2017: Journal of Molecular Graphics & Modelling
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