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Dihydroartemisinin

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https://www.readbyqxmd.com/read/28617435/interaction-between-autophagy-and-senescence-is-required-for-dihydroartemisinin-to-alleviate-liver-fibrosis
#1
Zili Zhang, Zhen Yao, Shifeng Zhao, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Autophagy and cellular senescence are stress responses essential for homeostasis. Therefore, they may represent new pharmacologic targets for drug development to treat diseases. In this study, we sought to evaluate the effect of dihydroartemisinin (DHA) on senescence of activated hepatic stellate cells (HSCs), and to further elucidate the underlying mechanisms. We found that DHA treatment induced the accumulation of senescent activated HSCs in rat fibrotic liver, and promoted the expression of senescence markers p53, p16, p21 and Hmga1 in cell model...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615016/ex-vivo-susceptibility-and-genotyping-of-plasmodium-falciparum-isolates-from-pikine-senegal
#2
Aminata Mbaye, Amy Gaye, Baba Dieye, Yaye D Ndiaye, Amy K Bei, Muna Affara, Awa B Deme, Mamadou S Yade, Khadim Diongue, Ibrahima M Ndiaye, Tolla Ndiaye, Mouhamed Sy, Ngayo Sy, Ousmane Koita, Donald J Krogstad, Sarah Volkman, Davis Nwakanma, Daouda Ndiaye
BACKGROUND: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006...
June 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28556586/dihydroartemisinin-piperaquine-versus-artesunate-amodiaquine-for-treatment-of-malaria-infection-in-pregnancy-in-ghana-an-open-label-randomized-non-inferiority-trial
#3
Joseph Osarfo, Harry Tagbor, Matthew Cairns, Michael Alifrangis, Pascal Magnussen
OBJECTIVE: To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy. METHODS: 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomized to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-weeks post-partum to ascertain the health status of the babies...
May 28, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28539634/the-plasmodium-pi-4-k-inhibitor-kdu691-selectively-inhibits-dihydroartemisinin-pretreated-plasmodium-falciparum-ring-stage-parasites
#4
L Dembele, X Ang, M Chavchich, G M C Bonamy, J J Selva, M Yi-Xiu Lim, C Bodenreider, B K S Yeung, F Nosten, B M Russell, M D Edstein, J Straimer, D A Fidock, T T Diagana, P Bifani
Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539125/do-anti-malarials-in-africa-meet-quality-standards-the-market-penetration-of-non-quality-assured-artemisinin-combination-therapy-in-eight-african-countries
#5
Paul N Newton, Kara Hanson, Catherine Goodman
BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector...
May 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28537265/a-tetraoxane-based-antimalarial-drug-candidate-that-overcomes-pfk13-c580y-dependent-artemisinin-resistance
#6
Paul M O'Neill, Richard K Amewu, Susan A Charman, Sunil Sabbani, Nina F Gnädig, Judith Straimer, David A Fidock, Emma R Shore, Natalie L Roberts, Michael H-L Wong, W David Hong, Chandrakala Pidathala, Chris Riley, Ben Murphy, Ghaith Aljayyoussi, Francisco Javier Gamo, Laura Sanz, Janneth Rodrigues, Carolina Gonzalez Cortes, Esperanza Herreros, Iñigo Angulo-Barturén, María Belén Jiménez-Díaz, Santiago Ferrer Bazaga, María Santos Martínez-Martínez, Brice Campo, Raman Sharma, Eileen Ryan, David M Shackleford, Simon Campbell, Dennis A Smith, Grennady Wirjanata, Rintis Noviyanti, Ric N Price, Jutta Marfurt, Michael J Palmer, Ian M Copple, Amy E Mercer, Andrea Ruecker, Michael J Delves, Robert E Sinden, Peter Siegl, Jill Davies, Rosemary Rochford, Clemens H M Kocken, Anne-Marie Zeeman, Gemma L Nixon, Giancarlo A Biagini, Stephen A Ward
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28535793/intermittent-preventive-treatment-for-malaria-among-children-in-a-refugee-camp-in-northern-uganda-lessons-learned
#7
Matthew E Coldiron, Estrella Lasry, Malika Bouhenia, Debashish Das, Peter Okui, Dan Nyehangane, Juliet Mwanga, Celine Langendorf, Greg Elder, Léon Salumu, Rebecca F Grais
Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin-piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home...
May 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28526807/dihydroartemisinin-induces-autophagy-dependent-death-in-human-tongue-squamous-cell-carcinoma-cells-through-dna-double-strand-break-mediated-oxidative-stress
#8
Xinli Shi, Li Wang, Xiaoming Li, Jing Bai, Jianchun Li, Shenghao Li, Zeming Wang, Mingrui Zhou
Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511713/artemisinin-based-combination-therapy-in-pregnant-women-in-zambia-efficacy-safety-and-risk-of-recurrent-malaria
#9
Michael Nambozi, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, David Mwakazanga, Joyce Mulenga, Webster Kasongo, Jozefien Buyze, Modest Mulenga, Jean-Pierre Van Geertruyden, Umberto D'Alessandro
BACKGROUND: In Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, the World Health Organization recommends the use of artemisinin-based combination therapy (ACT) in the second and third trimester of pregnancy. In a context of limited information on ACT, the safety and efficacy of three combinations, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS) and dihydroartemisinin-piperaquine (DHAPQ) were assessed in pregnant women with malaria...
May 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28506239/dihydroartemisinin-inhibits-tctp-dependent-metastasis-in-gallbladder-cancer
#10
Fei Zhang, Qiang Ma, Zihang Xu, Haibin Liang, Huaifeng Li, Yuanyuan Ye, Shanshan Xiang, Yijian Zhang, Lin Jiang, Yunping Hu, Zheng Wang, Xuefeng Wang, Yong Zhang, Wei Gong, Yingbin Liu
BACKGROUND: Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer. METHODS: Levels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins...
May 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28498397/dihydroartemisinin-inhibits-the-viability-of-cervical-cancer-cells-by-upregulating-caveolin%C3%A2-1-and-mitochondrial-carrier-homolog%C3%A2-2-involvement-of-p53-activation-and-nad-p-h-quinone-oxidoreductase%C3%A2-1-downregulation
#11
Ting Zhang, Yuan Hu, Ting Wang, Peiling Cai
Dihydroartemisinin (DHA) has been shown to inhibit the viability of various cancer cells. Previous studies have revealed that the mechanisms involved in the inhibitory effects of DHA are based on theactivation of p53 and the mitochondrial-related cell death pathway. However, the exact association between upstream signaling and the activation of cell death pathway remains unclear. In this study, we found that DHA treatment induced the upregulation of caveolin 1 (Cav1) and mitochondrial carrier homolog 2 (MTCH2) in HeLa cells, and this was associated with the DHA-induced inhibition of cell viability and DHA-induced apoptosis...
May 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28494763/artemisinin-resistance-without-pfkelch13-mutations-in-plasmodium-falciparum-isolates-from-cambodia
#12
Angana Mukherjee, Selina Bopp, Pamela Magistrado, Wesley Wong, Rachel Daniels, Allison Demas, Stephen Schaffner, Chanaki Amaratunga, Pharath Lim, Mehul Dhorda, Olivo Miotto, Charles Woodrow, Elizabeth A Ashley, Arjen M Dondorp, Nicholas J White, Dyann Wirth, Rick Fairhurst, Sarah K Volkman
BACKGROUND: Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance...
May 12, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28487425/a-variant-pfcrt-isoform-can-contribute-to-plasmodium-falciparum-resistance-to-the-first-line-partner-drug-piperaquine
#13
Satish K Dhingra, Devasha Redhi, Jill M Combrinck, Tomas Yeo, John Okombo, Philipp P Henrich, Annie N Cowell, Purva Gupta, Matthew L Stegman, Jonathan M Hoke, Roland A Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J Egan, David A Fidock
Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28480232/artemether-lumefantrine-and-dihydroartemisinin-piperaquine-exert-inverse-selective-pressure-on-plasmodium-falciparum-drug-sensitivity-associated-haplotypes-in-uganda
#14
Aimee R Taylor, Jennifer A Flegg, Chris C Holmes, Philippe J Guérin, Carol H Sibley, Melissa D Conrad, Grant Dorsey, Philip J Rosenthal
BACKGROUND: Altered sensitivity to multiple antimalarial drugs is mediated by polymorphisms in pfmdr1, which encodes the Plasmodium falciparum multidrug resistance transporter. In Africa the N86Y and D1246Y polymorphisms have been shown to be selected by treatment, with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) selecting for wild-type and mutant alleles, respectively. However, there has been little study of pfmdr1 haplotypes, in part because haplotype analyses are complicated by multiclonal infections...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28479604/codelivery-of-dihydroartemisinin-and-doxorubicin-in-mannosylated-liposomes-for-drug-resistant-colon-cancer-therapy
#15
Xue-Jia Kang, Hui-Yuan Wang, Hui-Ge Peng, Bin-Fan Chen, Wen-Yuan Zhang, Ai-Hua Wu, Qin Xu, Yong-Zhuo Huang
Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes)...
June 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28460112/baseline-in-vivo-ex-vivo-and-molecular-responses-of-plasmodium-falciparum-to-artemether-and-lumefantrine-in-three-endemic-zones-for-malaria-in-colombia
#16
Samanda Aponte, Ángela Patricia Guerra, Catalina Álvarez-Larrotta, Sindy Durley Bernal, César Restrepo, Camila González, María Fernanda Yasnot, Angélica Knudson-Ospina
Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days...
February 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28449690/daily-home-fortification-with-iron-as-ferrous-fumarate-versus-nafeedta-a-randomised-placebo-controlled-non-inferiority-trial-in-kenyan-children
#17
Emily M Teshome, Pauline E A Andang'o, Victor Osoti, Sofie R Terwel, Walter Otieno, Ayşe Y Demir, Andrew M Prentice, Hans Verhoef
BACKGROUND: We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. METHODS: We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L...
April 28, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28427409/efficacies-of-dha-ppq-and-as-sp-in-patients-with-uncomplicated-plasmodium-falciparum-malaria-in-an-area-of-an-unstable-seasonal-transmission-in-sudan
#18
Abdelrahim O Mohamed, Muzamil M Abdel Hamid, Omer S Mohamed, Nuha S Elkando, Abdelmaroof Suliman, Mariam A Adam, Fahad Awad Ali Elnour, Elfatih M Malik
BACKGROUND: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28400526/plasmodium-falciparum-k13-mutations-differentially-impact-ozonide-susceptibility-and-parasite-fitness-in-vitro
#19
Judith Straimer, Nina F Gnädig, Barbara H Stokes, Michelle Ehrenberger, Audrey A Crane, David A Fidock
The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based combination therapies (ACTs), underscore the urgent need to identify suitable replacement drugs. Discovery and development efforts have identified a series of ozonides with attractive chemical and pharmacological properties that are being touted as suitable replacements. Partial resistance to ART, defined as delayed parasite clearance in malaria patients treated with an ART derivative or an ACT, has been associated with mutations in the P...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28388902/therapeutic-efficacy-and-artemisinin-resistance-in-northern-myanmar-evidence-from-in-vivo-and-molecular-marker-studies
#20
Moe Kyaw Myint, Charlotte Rasmussen, Aung Thi, Dorina Bustos, Pascal Ringwald, Khin Lin
BACKGROUND: In Myanmar, three types of artemisinin-based combination therapy (ACT) are recommended as first-line treatment of uncomplicated falciparum malaria: artemether-lumefantrine (AL), artesunate-mefloquine (AS + MQ), and dihydroartemisinin-piperaquine (DP). Resistance to both artemisinins and ACT partner drugs has been reported from the Greater Mekong Sub-region, and regular efficacy monitoring of the recommended ACT is conducted in Myanmar. This paper reports on results from studies to monitor the efficacy of the three forms of ACT in sentinel sites in northern Myanmar, and investigations of mutations in the Kelch13 (k13) propeller domain...
April 7, 2017: Malaria Journal
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