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Artemisinin

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https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#1
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27900057/in-vitro-and-in-vivo-inhibition-of-tumor-cell-viability-by-combined-dihydroartemisinin-and-doxorubicin-treatment-and-the-underlying-mechanism
#2
Xiang Tai, Xiao-Bei Cai, Zhang Zhang, Rui Wei
The natural extract artemisinin and its derivatives have good anticancer activity. The present study aimed to investigate the in vitro inhibitory effects of combined dihydroartemisinin (DHA) and doxorubicin (DOX) treatment on a variety of tumor cell lines (HeLa, OVCAR-3, MCF-7, PC-3 and A549), as well as the underlying mechanisms. In addition, the in vivo effects of DHA and DOX were evaluated using a mouse HeLa tumor model. The HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells were treated with a combination of DHA and DOX, and the effect on cell viability was detected by Cell Counting kit-8...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899115/characterizing-the-impact-of-sustained-sulfadoxine-pyrimethamine-use-upon-the-plasmodium-falciparum-population-in-malawi
#3
Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri, Anja Terlouw, Alister Craig, Susana Campino, Harold Ocholla, Taane G Clark
BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used...
November 29, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27897259/artemisinin-analogue-sm934-attenuate-collagen-induced-arthritis-by-suppressing-t-follicular-helper-cells-and-t-helper-17-cells
#4
Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895848/four-artemisinin-based-treatments-in-african-pregnant-women-with-malaria
#5
Divine Pekyi, Akua A Ampromfi, Halidou Tinto, Maminata Traoré-Coulibaly, Marc C Tahita, Innocent Valéa, Victor Mwapasa, Linda Kalilani-Phiri, Gertrude Kalanda, Mwayiwawo Madanitsa, Raffaella Ravinetto, Theonest Mutabingwa, Prosper Gbekor, Harry Tagbor, Gifty Antwi, Joris Menten, Maaike De Crop, Yves Claeys, Celine Schurmans, Chantal Van Overmeir, Kamala Thriemer, Jean-Pierre Van Geertruyden, Umberto D'Alessandro, Michael Nambozi, Modest Mulenga, Sebastian Hachizovu, Jean-Bertin B Kabuya, Joyce Mulenga
BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine...
September 2016: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/27895526/development-of-a-simple-and-specific-direct-competitive-elisa-for-the-determination-of-artesunate-using-an-anti-artesunate-polyclonal-antiserum
#6
Yoshinori Mitsui
BACKGROUND: Since artesunate (ART) became a vital component of artemisinin (ARM)-based combination therapies for the treatment for malaria, counterfeit ART drugs have spread in regions of Southeast Asia and Africa. The consumption of counterfeit ART drugs has resulted in the death of many patients. Thus, evaluating the quality of ART drugs is needed. There are several methods for quantitating the ART content in tablets, the most common being a high-performance liquid chromatography. However, that method is hampered by the need for expensive equipment and a rather time-consuming process of extraction...
2016: Tropical Medicine and Health
https://www.readbyqxmd.com/read/27895269/stability-of-dihydroartemisinin-piperaquine-tablet-halves-during-prolonged-storage-under-tropical-conditions
#7
Eva Maria Hodel, Harparkash Kaur, Dianne J Terlouw
Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27894908/implication-of-artemisinin-nematocidal-activity-on-experimental-trichinellosis-in-vitro-and-in-vivo-studies
#8
Dina M Abou Rayia, Abeer E Saad, Dalia S Ashour, Radwa M Oreiby
Benzimidazole drugs are used for treatment of trichinellosis, but they have a limited effect against encapsulated larval stages of Trichinella spiralis. Hence, there is a considerable interest in developing new anthelmintic drugs. Our aim is to investigate the possible effect of artemisinin on T. spiralis in in vitro and in vivo studies. T. spiralis worms were isolated from infected mice and transferred to 3 culture media; group I: with no drugs, group II: contained artemisinin and group III: contained mebendazole, then they were subjected to electron microscopic study...
November 25, 2016: Parasitology International
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#9
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27886547/comprehensive-review-on-various-strategies-for-antimalarial-drug-discovery
#10
Mitali Mishra, Vikash K Mishra, Varsha Kashaw, Arun K Iyer, Sushil Kumar Kashaw
The resistance of malaria parasites to existing drugs carries on growing and progressively limiting our ability to manage this severe disease and finally lead to a massive global health burden. Till now, malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. Very few new antimalarials were developed in the past 50 years. Among recent approaches, identification of novel chemotherapeutic targets, exploration of natural products with medicinal significance, covalent bitherapy having a dual mode of action into a single hybrid molecule and malaria vaccine development are explored heavily...
November 12, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27881136/community-health-workers-adherence-to-referral-guidelines-evidence-from-studies-introducing-rdts-in-two-malaria-transmission-settings-in-uganda
#11
Sham Lal, Richard Ndyomugenyi, Lucy Paintain, Neal D Alexander, Kristian S Hansen, Pascal Magnussen, Daniel Chandramohan, Siân E Clarke
BACKGROUND: Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline...
November 24, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27872816/evidence-of-triple-mutant-pfdhps-isgnga-haplotype-in-plasmodium-falciparum-isolates-from-north-east-india-an-analysis-of-sulfadoxine-resistant-haplotype-selection
#12
Manuj K Das, Sumi Chetry, Mohan C Kalita, Prafulla Dutta
BACKGROUND: North-east region of India has consistent role in the spread of multi drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After rapid clinical treatment failure of Artemisinin based combination therapy-Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine (ACT-AL) combination therapy was introduced in the year 2012 in this region for the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based polymorphism analysis, seven codons of P...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27872070/estimation-of-the-in-vivo-minimum-inhibitory-concentration-of-cipargamin-in-uncomplicated-plasmodium-falciparum-malaria
#13
Hien Tinh Tran, Nicholas J White, Thuy-Nhien Thanh Nguyen, Hoa Thi Nhu, Thuan Duc Phung, Joel Tarning, François Nosten, Baldur Magnusson, Jay Prakash Jain, Kamal Hamed
The minimum inhibitory concentration (MIC) of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. To ensure cure of malaria the MIC must be exceeded until all parasites have been eliminated. The development of highly sensitive and accurate polymerase chain reaction quantitation of low-density malaria parasitemia enables prospective pharmacokinetic-pharmacodynamic (PK-PD) characterization of antimalarial drug effects, and now allows identification of the in-vivo MIC...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27867026/artemisinin-and-its-derivatives-in-treating-protozoan-infections-beyond-malaria
#14
REVIEW
Cecilia Shi Ni Loo, Nelson Siu Kei Lam, Deying Yu, Xin-Zhuan Su, Fangli Lu
Many parasitic protozoan diseases continue to rank among the world's greatest global health problems, which are also common among poor populations. Currently available drugs for treatment present drawbacks, urging the need for more effective, safer, and cheaper drugs. Artemisinin (ART) and its derivatives are some of the most important classes of antimalarial agents originally derived from Artemisia annua L. However, besides the outstanding antimalarial and antischistosomal activities, ART and its derivatives also possess activities against other parasitic protozoa...
November 17, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27865890/safety-tolerability-and-efficacy-of-repeated-doses-of-dihydroartemisinin-piperaquine-for-prevention-and-treatment-of-malaria-a-systematic-review-and-meta-analysis
#15
Julie Gutman, Stephanie Kovacs, Grant Dorsey, Andy Stergachis, Feiko O Ter Kuile
BACKGROUND: Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP. METHODS: Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ"...
November 16, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27860262/ferroptosis-a-new-form-of-cell-death-and-its-relationships-with-tumourous-diseases
#16
REVIEW
Haitao Yu, Pengyi Guo, Xiaozai Xie, Yi Wang, Gang Chen
Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system Xc(-) inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e...
November 10, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27856948/impact-of-introducing-subsidized-combination-treatment-with-artemether-lumefantrine-on-sales-of-anti-malarial-monotherapies-a-survey-of-private-sector-pharmacies-in-huambo-angola
#17
Cristina Lussiana, Marco Floridia, Joana Martinho do Rosário, Filomeno Fortes, Richard Allan
BACKGROUND: Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. METHODS: Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses...
November 17, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27853513/south-east-asian-strains-of-plasmodium-falciparum-display-higher%C3%A2-ratio-of-non-synonymous-to-synonymous-polymorphisms-compared-to-african-strains
#18
Gajinder Pal Singh, Amit Sharma
Resistance to frontline anti-malarial drugs, including artemisinin, has repeatedly arisen in South-East Asia, but the reasons for this are not understood. Here we test whether evolutionary constraints on Plasmodium falciparum strains from South-East Asia differ from African strains. We find a significantly higher ratio of non-synonymous to synonymous polymorphisms in P. falciparum from South-East Asia compared to Africa, suggesting differences in the selective constraints on P. falciparum genome in these geographical regions...
2016: F1000Research
https://www.readbyqxmd.com/read/27843298/endoperoxide-antimalarials-development-structural-diversity-and-pharmacodynamic-aspects-with-reference-to-1-2-4-trioxane-based-structural-scaffold
#19
REVIEW
Mithun Rudrapal, Dipak Chetia
Malaria disease continues to be a major health problem worldwide due to the emergence of multidrug-resistant strains of Plasmodium falciparum. In recent days, artemisinin (ART)-based drugs and combination therapies remain the drugs of choice for resistant P. falciparum malaria. However, resistance to ART-based drugs has begun to appear in some parts of the world. Endoperoxide compounds (natural/semisynthetic/synthetic) representing a huge number of antimalarial agents possess a wide structural diversity with a desired antimalarial effectiveness against resistant P...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27825878/an-artemisinin-mediated-ros-evolving-and-dual-protease-light-up-nanocapsule-for-real-time-imaging-of-lysosomal-tumor-cell-death
#20
Liwei Huang, Yingping Luo, Xian Sun, Huangxian Ju, Jiangwei Tian, Bo-Yang Yu
Lysosomes are critical organelles for cellular homeostasis and can be used as potential targets to kill tumor cells from inside. Many photo-therapeutic methods have been developed to overproduce reactive oxygen species (ROS) to trigger lysosomal membrane permeabilization (LMP)-associated cell death pathway. However, these technologies rely on extra irradiation to activate the photosensitizers, which limits the applications in treating deep seated tumors and widespread metastatic lesions. This work reports a multifunctional nanocapsule to achieve targeted lysosomal tumor cell death without irradiation and real-time monitoring of drug effect through encapsulating artemisinin and dual protease light-up nanoprobe in a folate-functionalized liposome...
October 11, 2016: Biosensors & Bioelectronics
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