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https://www.readbyqxmd.com/read/28302108/confirmation-of-plasmodium-falciparum-in-vitro-resistance-to-monodesethylamodiaquine-and-chloroquine-in-dakar-senegal-in-2015
#1
Silman Diawara, Marylin Madamet, Mame Bou Kounta, Gora Lo, Khalifa Ababacar Wade, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
BACKGROUND: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28302017/targeting-pyrimidine-pathway-of-plasmodium-knowlesi-new-strategies-towards-identification-of-novel-antimalarial-chemotherapeutic-agents
#2
Mayank Rashmi, Manoj Kumar Yadav, D Swati
Plasmodium knowlesi has been recently recognized as a human malarial parasite, particularly in the region of south-east Asia. The effective prevention and treatment of this disease is increasingly bound to fail due to the emergence of drug resistance. Hence, design of new drugs against known targets is gaining importance. Pyrimidine pathway is a crucial metabolic pathway in P. knowlesi, and the enzymes involved are also unique in terms of their structure and function as compared to its human counterpart. Thus targeting Dihydroorotase, an enzyme involved in the pyrimidine pathway, provides a promising route for novel drug development...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28294321/artesunate-inhibits-rankl-induced-osteoclastogenesis-and-bone-resorption-in-vitro-and-prevents-lps-induced-bone-loss-in-vivo
#3
Cheng-Ming Wei, Qian Liu, Fang-Ming Song, Xi-Xi Lin, Yi-Ji Su, Jiake Xu, Lin Huang, Shao-Hui Zong, Jin-Min Zhao
Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs)...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28292906/parasitophorous-vacuole-poration-precedes-its-rupture-and-rapid-host-erythrocyte-cytoskeleton-collapse-in-plasmodium-falciparum-egress
#4
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/28288632/unexpected-selections-of-plasmodium-falciparum-polymorphisms-in-previously-treatment-na%C3%A3-ve-areas-after-monthly-presumptive-administration-of-three-different-anti-malarial-drugs-in-liberia-1976-78
#5
Irina T Jovel, Anders Björkman, Cally Roper, Andreas Mårtensson, Johan Ursing
BACKGROUND: To assess the effect on malaria prevalence, village specific monthly administrations of pyrimethamine, chlorproguanil, chloroquine or placebo were given to children in four previously treatment-naïve Liberian villages, 1976-78. Plasmodium falciparum in vivo resistance developed to pyrimethamine only. Selection of molecular markers of P. falciparum resistance after 2 years of treatment are reported. METHODS: Blood samples were collected from 191 study children in a survey in 1978...
March 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28283009/-production-and-molecular-characterization-of-plasmodium-falciparum-recombinant-circumsporozoite-protein-with-37-nanp-and-4-nvdp-epitopes
#6
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/28279619/led-fluorescence-microscopy-novel-method-for-malaria-diagnosis-compared-with-routine-methods
#7
Riddhi Hathiwala, Preeti R Mehta, Gita Nataraj, Siddhi Hathiwala
Rapid and accurate diagnosis of malaria is the need of hour for effective management and controlling drug resistance. The conventional and gold-standard method, Light microscopy (LM), is time-consuming, requires trained staff and well-maintained equipments. The newly developed, rapid diagnostic tests (RDT) are fast and reliable, but give only qualitative results, are expensive and have short shelf life. Light Emission Diode fluorescence microscopy (LED FM) may provide a reliable alternative which can be used for routine diagnosis...
March 6, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28279180/primaquine-thiazolidinones-block-malaria-transmission-and-development-of-the-liver-exoerythrocytic-forms
#8
Anna Caroline C Aguiar, Flávio Jr B Figueiredo, Patrícia D Neuenfeldt, Tony H Katsuragawa, Bruna B Drawanz, Wilson Cunico, Photini Sinnis, Fidel Zavala, Antoniana U Krettli
BACKGROUND: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. RESULTS: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro...
March 9, 2017: Malaria Journal
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
#9
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/28268096/impact-of-long-lasting-insecticidal-nets-on-prevalence-of-subclinical-malaria-among-children-in-the-presence-of-pyrethroid-resistance-in-anopheles-culicifacies-in-central-india
#10
Mehul Kumar Chourasia, Raghavendra Kamaraju, Immo Kleinschmidt, Rajendra M Bhatt, Dipak Kumar Swain, Tessa Bellamy Knox, Neena Valecha
BACKGROUND: Subclinical (asymptomatic) cases of malaria could be a major barrier to the success of malaria elimination programs. This study has evaluated the impact of long-lasting insecticidal nets (LLINs) on the prevalence of subclinical malaria in the presence of pyrethroid resistance in the main malaria vector Anopheles culicifacies on malaria transmission among a cohort of children in villages of the Keshkal sub-district in Chhattisgarh state. METHODS: A cohort of 6582 children ages less than 14 years was enrolled from 80 study clusters...
March 6, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28267260/comparative-transcriptomic-analysis-of-key-genes-involved-in-flavonoid-biosynthetic-pathway-and-identification-of-a-flavonol-synthase-from-artemisia-annua-l
#11
Shuoqian Liu, Liping Liu, Yuwei Tang, Shuo Xiong, Jinhua Long, Zhonghua Liu, Na Tian
(1) The regulation mechanism of flavonoids, which were found to synergize anti-malarial and anti-cancer compounds in Artemisia annua, is still unclear. (2) In this study, an anthocyanidin-accumulating mutant callus was induced from A. annua, and then comparative transcriptomic analysis of the wild-type and mutant calli was performed, based on the next-generation Illumina/Solexa sequencing platform and de novo assembly. (3) As a result, a total of 82,393 unigenes were obtained and 34,764 unigenes were annotated in the public database...
March 7, 2017: Plant Biology
https://www.readbyqxmd.com/read/28267183/isolation-and-structure-elucidation-of-natural-products-of-three-soft-corals-and-a-sponge-from-the-coast-of-madagascar
#12
Marie Pascaline Rahelivao, Tilo Lübken, Margit Gruner, Olga Kataeva, Rahanira Ralambondrahety, Hanta Andriamanantoanina, Marek P Checinski, Ingmar Bauer, Hans-Joachim Knölker
We investigated the three soft corals Sarcophyton stellatum, Capnella fungiformis and Lobophytum crassum and the sponge Pseudoceratina arabica, which have been collected at the coast of Madagascar. In addition to previously known marine natural products, S. stellatum provided the new (+)-enantiomer of the cembranoid (1E,3E,11E)-7,8-epoxycembra-1,3,11,15-tetraene (2). Capnella fungiformis afforded three new natural products, ethyl 5-[(1E,5Z)-2,6-dimethylocta-1,5,7-trienyl]furan-3-carboxylate (6), ethyl 5-[(1E,5E)-2,6-dimethylocta-1,5,7-trienyl]furan-3-carboxylate (7) and the diepoxyguaiane sesquiterpene oxyfungiformin (9a)...
March 7, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28260517/capi-computational-model-for-apicoplast-inhibitors-prediction-against-plasmodium-parasite
#13
Surabhi Dixit, Deepak Singla
Background Discovery of apicoplast as a drug target offers a new direction in the development of novel anti-malarial compounds, especially against the drug-resistant strains. Drugs such as azithromycin were reported to block the apicoplast development that leads to unusual phenotypes affecting the parasite. This phenomenon suggeststhat identification of new apicoplast inhibitors will aid in the anti-malarial drug discovery. Therefore, in this study, we developed a computational model to predict apicoplast inhibitors by applying state-of-the-art machine learning techniques...
March 1, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28259160/in-vivo-efficacy-of-top-five-surveyed-ghanaian-herbal-anti-malarial-products
#14
Dennis Wilmot, Elvis Ofori Ameyaw, Daniel Amoako-Sakyi, Johnson Nyarko Boampong, Neils Ben Quashie
BACKGROUND: Anti-malarial herbal preparations (HPs) continue to enjoy high patronage in Ghana despite reports that the artemisinin-based combination therapy (ACT), the recommended first choice for treatment of uncomplicated malaria in the country, remains efficacious. A major issue with the use of these preparations is inadequate or unreliable data on their efficacy and quality. An assessment of the potency and quality of the most popular commercial anti-malarial HPs in Ghana was, therefore, carried out...
March 4, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28259152/should-chemoprophylaxis-be-a-main-strategy-for-preventing-re-introduction-of-malaria-in-highly-receptive-areas-sri-lanka-a-case-in-point
#15
A Rajitha Wickremasinghe, Renu Wickremasinghe, Hemantha D B Herath, S Deepika Fernando
BACKGROUND: Imported malaria cases continue to be reported in Sri Lanka, which was declared 'malaria-free' by the World Health Organization in September 2016. Chemoprophylaxis, a recommended strategy for malaria prevention for visitors travelling to malaria-endemic countries from Sri Lanka is available free of charge. The strategy of providing chemoprophylaxis to visitors to a neighbouring malaria-endemic country within the perspective of a country that has successfully eliminated malaria but is highly receptive was assessed, taking Sri Lanka as a case in point...
March 4, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28258239/the-pushmi-pullyu-of-resistance-to-chloroquine-in-malaria
#16
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/28253937/therapeutic-indications-and-other-use-case-driven-updates-in-the-drug-ontology-anti-malarials-anti-hypertensives-opioid-analgesics-and-a-large-term-request
#17
William R Hogan, Josh Hanna, Amanda Hicks, Samira Amirova, Baxter Bramblett, Matthew Diller, Rodel Enderez, Timothy Modzelewski, Mirela Vasconcelos, Chris Delcher
BACKGROUND: The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication...
March 3, 2017: Journal of Biomedical Semantics
https://www.readbyqxmd.com/read/28252130/an-embedded-barcode-for-connected-malaria-rapid-diagnostic-tests
#18
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/28249591/controlled-release-of-artemisone-for-the-treatment-of-experimental-cerebral-malaria
#19
Jacob Golenser, Viola Buchholz, Amir Bagheri, Abed Nasereddin, Ron Dzikowski, Jintao Guo, Nicholas H Hunt, Sara Eyal, Natalia Vakruk, Andreas Greiner
BACKGROUND: Cerebral malaria (CM) is a leading cause of malarial mortality resulting from infection by Plasmodium falciparum. Treatment commonly involves adjunctive care and injections or transfusion of artemisinins. All artemisinins that are in current use are metabolized to dihydroxyartemisinin (DHA), to which there is already some parasite resistance. We used artemisone, a derivative that does not convert to DHA, has improved pharmacokinetics and anti-plasmodial activity and is also anti-inflammatory (an advantage given the immunopathological nature of CM)...
March 1, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28242687/quantification-of-labile-heme-in-live-malaria-parasites-using-a-genetically-encoded-biosensor
#20
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
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