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Dihydroartemisinin

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https://www.readbyqxmd.com/read/28105176/dihydroartemisinin-transiently-activates-the-jnk-sapk-signaling-pathway-in-endothelial-cells
#1
Fengyun Dong, Ju Han, Guoxian Jing, Xiaocui Chen, Suhua Yan, Longtao Yue, Zhiqun Cao, Xiaochun Liu, Guozhao Ma, Ju Liu
Artemisinin and its derivatives are well-known anti-malaria drugs and in the early stages of research for cancer treatment. Dihydroartemisinin (DHA), a more water-soluble derivative of artemisinin, has demonstrated strong anti-angiogenic activity. The purpose of the present study was to investigate the underlying molecular mechanisms of the effect of DHA on angiogenesis. Human umbilical vein endothelial cells (HUVECs) treated with DHA were examined for apoptosis and activation of the c-Jun N-terminal kinase (JNK) signaling pathway, one of the major mitogen-activated protein kinase cascades...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#2
Peng Cao, Dongjin Leng, Ying Li, Ziwei Zhang, Lei Liu, Xiaoyan Li
Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe(3+) than normal cells, there are a large number of transferrin receptors on the tumor cell membrane...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28086775/rapid-decline-in-the-susceptibility-of-plasmodium-falciparum-to-dihydroartemisinin-piperaquine-in-the-south-of-vietnam
#3
Ngo Viet Thanh, Nguyen Thuy-Nhien, Nguyen Thi Kim Tuyen, Nguyen Thanh Tong, Nguyen Thuy Nha-Ca, Le Thanh Dong, Huynh Hong Quang, Jeremy Farrar, Guy Thwaites, Nicholas J White, Marcel Wolbers, Tran Tinh Hien
BACKGROUND: Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. METHODS: In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up...
January 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28072872/population-pharmacokinetic-properties-of-piperaquine-in-falciparum-malaria-an-individual-participant-data-meta-analysis
#4
Richard M Hoglund, Lesley Workman, Michael D Edstein, Nguyen Xuan Thanh, Nguyen Ngoc Quang, Issaka Zongo, Jean Bosco Ouedraogo, Steffen Borrmann, Leah Mwai, Christian Nsanzabana, Ric N Price, Prabin Dahal, Nancy C Sambol, Sunil Parikh, Francois Nosten, Elizabeth A Ashley, Aung Pyae Phyo, Khin Maung Lwin, Rose McGready, Nicholas P J Day, Philippe J Guerin, Nicholas J White, Karen I Barnes, Joel Tarning
BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#5
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28059831/effect-of-dihydroartemisinin-on-uhrf1-gene-expression-in-human-prostate-cancer-pc-3-cells
#6
Shijuan Du, Ge Xu, Wenqin Zou, Tingxiu Xiang, Ziguo Luo
As the second most common cancer in men around the world, prostate cancer is increasingly gaining more attention. Dihydroartemisinin (DHA) has been proven to be a promising anticancer agent in vitro as well as in vivo in accumulating data. However, the detailed mechanisms of how DHA action in human prostate cancer PC-3 cells remain elusive. This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28044042/influence-of-the-pfmdr1-gene-on-in-vitro-sensitivities-of-piperaquine-in-thai-isolates-of-plasmodium-falciparum
#7
Mathirut Mungthin, Ekularn Watanatanasup, Naruemon Sitthichot, Nantana Suwandittakul, Rommanee Khositnithikul, Stephen A Ward
Piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in Thailand. The aim of this study was to determine the in vitro sensitivity of Thai Plasmodium falciparum isolates against piperaquine and the influence of the pfmdr1 gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates of P. falciparum were accessed for in vitro piperaquine sensitivity...
January 2, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28039388/efficacy-and-safety-of-artesunate-mefloquine-therapy-for-treating-uncomplicated-plasmodium-falciparum-malaria-systematic-review-and-meta-analysis
#8
REVIEW
Henry Maia Peixoto, Paola Barbosa Marchesini, Maria Regina Fernandes de Oliveira
INTRODUCTION: The present study is a systematic review of the literature on the efficacy and safety of the treatment of uncomplicated Plasmodium falciparum infections with artesunate-mefloquine (ASMQ) compared to other artemisinin-based combination therapies (ACTs), designed to assist decision makers in Brazil. METHODS: Twenty-four randomized controlled trials (RCTs) were selected in four electronic databases and in complementary sources. Meta-analyses were performed to evaluate the efficacy expressed by relative risks (RR) obtained from treatment failure confirmed by the PCR...
December 29, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28032463/developmental-toxicity-studies-of-lumefantrine-and-artemether-in-rats-and-rabbits
#9
Robert L Clark, Maureen Youreneff, Anthony M DeLise
The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public...
December 2016: Birth Defects Research. Part B, Developmental and Reproductive Toxicology
https://www.readbyqxmd.com/read/28028628/risk-of-drug-resistance-in-plasmodium-falciparum-malaria-therapy-a-systematic-review-and-meta-analysis
#10
Li-Juan Zhou, Jing Xia, Hai-Xia Wei, Xiao-Jun Liu, Hong-Juan Peng
Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases...
December 27, 2016: Parasitology Research
https://www.readbyqxmd.com/read/28018925/parasite-clearance-and-artemether-pharmacokinetics-parameters-over-the-course-of-artemether-lumefantrine-treatment-for-malaria-in-human-immunodeficiency-virus-hiv-infected-and-hiv-uninfected-ugandan-children
#11
Richard Kajubi, Liusheng Huang, Moses Were, Sylvia Kiconco, Fangyong Li, Florence Marzan, David Gingrich, Myaing M Nyunt, Joshua Ssebuliba, Norah Mwebaza, Francesca T Aweeka, Sunil Parikh
BACKGROUND: Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized. METHODS: Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL)...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27999014/a-validated-bioluminescence-based-assay-for-the-rapid-determination-of-the-initial-rate-of-kill-for-discovery-antimalarials
#12
Imran Ullah, Raman Sharma, Giancarlo A Biagini, Paul Horrocks
OBJECTIVES: A future treatment for uncomplicated malaria will contain at least one component that exerts a rapid rate of kill. We describe here the validation and application of a simple, robust and rapid bioluminescence-based assay for the determination of the initial rate of kill in intra-erythrocytic asexual stages of Plasmodium falciparum METHODS: A modification to the concentration-response bioluminescence [here termed bioluminescence relative rate of kill (BRRoK)] assay, utilizing exposure to fold-IC50 concentrations (0...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27989749/ros-jnk1-2-dependent-activation-of-autophagy-is-required-for-the-induction-of-anti-inflammatory-effect-of-dihydroartemisinin-in-liver-fibrosis
#13
Zili Zhang, Mei Guo, Shifeng Zhao, Jiangjuan Shao, Shizhong Zheng
Accumulating evidence identifies autophagy as an inflammation-related defensive mechanism against diseases including liver fibrosis. Therefore, autophagy may represent a new pharmacologic target for drug development to treat liver fibrosis. In this study, we sought to investigate the effect of dihydroartemisinin (DHA) on autophagy, and to further examine the molecular mechanisms of DHA-induced anti-inflammatory effects. We found that DHA appeared to play an essential role in controlling excessive inflammation...
October 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27973923/prevention-and-control-of-malaria-in-pregnancy-new-threats-new-opportunities
#14
Stephen J Rogerson, Holger W Unger
Over 100 million women and their babies are at risk of malaria in pregnancy each year. Malaria prevention in pregnancy relies on long-lasting insecticidal nets (LLINs), and, in Africa, intermittent preventive treatment in pregnancy (IPTp). Increasing resistance of malaria parasites to sulfadoxine-pyrimethamine, the only drug endorsed for IPTp, and increasing mosquito resistance to pyrethroids used in LLINs, threaten the efficacy of these proven strategies, while operational challenges restrict their implementation in areas of great need...
December 23, 2016: Expert Review of Anti-infective Therapy
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
#15
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/27939985/dihydroartemisinin-protects-against-alcoholic-liver-injury-through-alleviating-hepatocyte-steatosis-in-a-farnesoid-x-receptor-dependent-manner
#16
Wenxuan Xu, Chunfeng Lu, Lu Yao, Feng Zhang, Jiangjuan Shao, Shizhong Zheng
Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies...
December 6, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27939426/preclinical-efficacy-and-safety-assessment-of-artemisinin-chemotherapeutic-agent-conjugates-for-ovarian-cancer
#17
Xiaoguang Li, Yu Zhou, Yanling Liu, Xu Zhang, Tao Chen, Kerong Chen, Qian Ba, Jingquan Li, Hong Liu, Hui Wang
: Artemisinin (ARS) and its derivatives, which are clinically used antimalarial agents, have shown antitumor activities. Their therapeutic potencies, however, are limited by their low solubility and poor bioavailability. Here, through a pharmacophore hybridization strategy, we synthesized ARS-drug conjugates, in which the marketed chemotherapeutic agents chlorambucil, melphalan, flutamide, aminoglutethimide, and doxifluridine, were separately bonded to Dihydroartemisinin (DHA) through various linkages...
December 2016: EBioMedicine
https://www.readbyqxmd.com/read/27928074/plasmodium-falciparum-resistance-to-artemisinin-derivatives-and-piperaquine-a-major-challenge-for-malaria-elimination-in-cambodia
#18
REVIEW
Valentine Duru, Benoit Witkowski, Didier Ménard
Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure...
December 7, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27923947/short-term-impact-of-mass-drug-administration-with-dihydroartemisinin-plus-piperaquine-on-malaria-in-southern-province-zambia-a-cluster-randomized-controlled-trial
#19
Thomas P Eisele, Adam Bennett, Kafula Silumbe, Timothy P Finn, Victor Chalwe, Mulakwa Kamuliwo, Busiku Hamainza, Hawela Moonga, Emmanuel Kooma, Elizabeth Chizema Kawesha, Joshua Yukich, Joseph Keating, Travis Porter, Ruben O Conner, Duncan Earle, Richard W Steketee, John M Miller
BACKGROUND:  Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS:  A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#20
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
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