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Suwanna Chaorattanakawee, Chanthap Lon, Krisada Jongsakul, Jariyanart Gawee, Somethy Sok, Siratchana Sundrakes, Nareth Kong, Chatchadaporn Thamnurak, Soklyda Chann, Sorayut Chattrakarn, Chantida Praditpol, Nillawan Buathong, Nichapat Uthaimongkol, Philip Smith, Narongrid Sirisopana, Rekol Huy, Satharath Prom, Mark M Fukuda, Delia Bethell, Douglas S Walsh, Charlotte Lanteri, David Saunders
BACKGROUND: The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. METHODS: Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai-Cambodian and Thai-Myanmar borders from 2010 to 2015...
October 21, 2016: Malaria Journal
Abdunoor M Kabanywanyi, Rita Baiden, Ali M Ali, Muhidin K Mahende, Bernhards R Ogutu, Abraham Oduro, Halidou Tinto, Margaret Gyapong, Ali Sie, Esperanca Sevene, Eusebio Macete, Seth Owusu-Agyei, Alex Adjei, Guillaume Compaoré, Innocent Valea, Isaac Osei, Abena Yawson, Martin Adjuik, Raymond Akparibo, Mwaka A Kakolwa, Salim Abdulla, Fred Binka
The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration...
2016: PloS One
Shoubing Wang, Ziran Xu
Increased eutrophication in the recent years has resulted in considerable research focus on identification of methods for preventing cyanobacterial blooms that are rapid and efficient. The objectives of this study were to investigate the effects of dihydroartemisinin and artemether on the growth of Microcystis aeruginosa and to elucidate its mode of action. Variations in cell density, chlorophyll a, soluble protein, malondialdehyde, extracellular alkaline phosphatase activity (APA), and chlorophyll fluorescence parameters (Fv/Fm, ΦPSII, ETR, rapid light curves, fast chlorophyll fluorescence curves on fluorescence intensity, and relative variable fluorescence) were evaluated by lab-cultured experiments...
2016: PloS One
Justin A Green, Khadeeja Mohamed, Navin Goyal, Samia Bouhired, Azra Hussaini, Siôn W Jones, Gavin C K W Koh, Ivan Kostov, Maxine Taylor, Allen Wolstenholm, Stephan Duparc
Tafenoquine is in development as a single-dose treatment for relapse prevention in Plasmodium vivax malaria. Tafenoquine must be co-administered with a blood schizonticide; either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine or artemether-lumefantrine. Healthy volunteers of either sex, aged 18-65 years, without glucose-6-phosphate dehydrogenase deficiency, were randomized into five cohorts (n=24 per cohort) to receive tafenoquine on day 1 (300 mg) plus: once daily dihydroartemisinin-piperaquine on days 1, 2 and 3 (120:960 mg for 36-<75 kg bodyweight; 160:1280 mg for ≥75-100 kg bodyweight); or artemether-lumefantrine (80:480 mg) two doses 8 h apart on day 1, then twice daily on days 2 and 3; or each drug given alone...
October 3, 2016: Antimicrobial Agents and Chemotherapy
Zenglei Wang, Mynthia Cabrera, Jingyun Yang, Lili Yuan, Bhavna Gupta, Xiaoying Liang, Karen Kemirembe, Sony Shrestha, Awtum Brashear, Xiaolian Li, Stephen F Porcella, Jun Miao, Zhaoqing Yang, Xin-Zhuan Su, Liwang Cui
Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide association studies, we investigated the associations of genome-wide single nucleotide polymorphisms with in vitro sensitivities to 10 commonly used antimalarial drugs in 94 P...
October 3, 2016: Scientific Reports
Ladda Kajeechiwa, May Myo Thwin, Paw Wah Shee, Nan Lin Yee, Elvina Elvina, Peapah Peapah, Kyawt Kyawt, Poe Thit Oo, William PoWah, Jacqueline Roger Min, Jacher Wiladphaingern, Lorenz von Seidlein, Suphak Nosten, Francois Nosten
BACKGROUND: A targeted malaria elimination project, including mass drug administrations (MDA) of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations...
September 27, 2016: Malaria Journal
Johan Ursing, Lars Rombo, Amabelia Rodrigues, Poul-Erik Kofoed
BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days to children aged 6 months-15 years with uncomplicated P...
2016: PloS One
Jean Baptiste Roseau, Bruno Pradines, Nicolas Paleiron, Serge Vedy, Marylin Madamet, Fabrice Simon, Emilie Javelle
BACKGROUND: Artemisinin-based combination therapy (ACT) introduced in the mid-1990s has been recommended since 2005 by the World Health Organization as first-line treatment against Plasmodium falciparum in all endemic countries. In 2010, the combination dihydroartemisinin-piperaquine (DP) was recommended for the treatment of uncomplicated P. falciparum malaria. DP is one of the first-line treatments used by the French army since 2013. CASE PRESENTATION: A case of P...
2016: Malaria Journal
Aiko Kume, Dang Trinh Minh Anh, Mototada Shichiri, Noriko Ishida, Hiroshi Suzuki
BACKGROUND: Artemisinin-based combination therapy (ACT) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. However, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with ACT. It means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. Therefore, the development of a new method to enhance the effect of artemisinin is required...
2016: Malaria Journal
Mwayiwawo Madanitsa, Linda Kalilani, Victor Mwapasa, Anna M van Eijk, Carole Khairallah, Doreen Ali, Cheryl Pace, James Smedley, Kyaw-Lay Thwai, Brandt Levitt, Duolao Wang, Arthur Kang'ombe, Brian Faragher, Steve M Taylor, Steve Meshnick, Feiko O Ter Kuile
BACKGROUND: In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP...
September 2016: PLoS Medicine
Dongdong Wang, Jiajia Zhou, Ruhui Chen, Ruohong Shi, Guoliang Xia, Shu Zhou, Zhenbang Liu, NianQing Zhang, Haibao Wang, Zhen Guo, Qianwang Chen
Dihydroartemisinin (DHA) has been investigated in cancer therapy for its reactive oxygen species (ROS) based cytotoxicity originated from interacting with ferrous ions that may reduce or eliminate the multidrug resistance commonly associated with conventional chemotherapy agents. However, synchronously delivery of hydrophobic DHA and Fe (Ⅲ) ions into tumor cells remains a major challenge. In this work, we develop novel Fe3O4@C@MIL-100(Fe) (FCM) nanoparticles for synchronously delivery of DHA and Fe (Ⅲ) for cancer therapy...
November 2016: Biomaterials
Yilong Li, Yongwei Wang, Rui Kong, Dongbo Xue, Shangha Pan, Hua Chen, Bei Sun
Despite improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate of only 8%. Therefore, novel strategies for prevention and treatment are urgently needed. Here, we investigated the mechanisms underlying the anti-pancreatic cancer effects dihydroartemisinin (DHA). Microarray and systematic analysis showed that DHA suppressed proliferation, inhibited angiogenesis and promoted apoptosis in two different human pancreatic cancer cell lines, and that 5 DHA-regulated microRNAs and 11 of their target mRNAs were involved in these effects via 19 microRNA-mRNA interactions...
August 23, 2016: Oncotarget
Jiao Zhang, Ling Guo, Xia Zhou, Fengyun Dong, Liqun Li, Zuowang Cheng, Yinghua Xu, Jiyong Liang, Qi Xie, Ju Liu
Angiogenesis is required for the growth and metastasis of solid tumors. The anti-malarial agent dihydroartemisinin (DHA) demonstrates potent anti-angiogenic activity, but the underlying molecular mechanisms are not yet fully understood. During the process of angiogenesis, endothelial cells migrating from existing capillaries may undergo programmed cell death after detaching from the extracellular matrix, a process that is defined as anchorage-dependent apoptosis or anoikis. In the present study, DHA-induced cell death was compared in human umbilical vein endothelial cells (HUVECs) cultured in suspension and attached to culture plates...
September 2016: Oncology Letters
Ruling Shen, Jun Li, Danrong Ye, Qingcheng Wang, Jian Fei
Onconase (Onc) is a cytotoxic ribonuclease derived from leopard frog oocytes or early embryos, and has been applied to the treatment of malignant mesothelioma in clinics. Onc also exhibits effective growth suppression of human non-small-cell lung cancer (NSCLC). Artemisinin (Art) and its derivatives are novel antimalarial drugs that exhibit antitumor and antivirus activities. In this study, we investigated the antitumor effects of combinations of Onc and an Art derivative, dihydroartemisinin (DHA), both in vitro and in vivo Isobologram analyses showed synergistic effects on the proliferation of NSCLC cells under the treatment with Onc and DHA...
October 2016: Acta Biochimica et Biophysica Sinica
Grégoire Falq, Rafael Van Den Bergh, Martin De Smet, William Etienne, Chea Nguon, Huy Rekol, Mallika Imwong, Arjen Dondorp, Jean-Marie Kindermans
BACKGROUND: In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented. METHODS: A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014...
2016: Malaria Journal
Sarah O'Neill, Susan Dierickx, Joseph Okebe, Edgard Dabira, Charlotte Gryseels, Umberto d'Alessandro, Koen Peeters Grietens
BACKGROUND: Clinical trials require high levels of participation and low drop-out rates to be successful. However, collecting blood samples from individuals recruited into clinical trials can be challenging when there is reticence about blood-taking. In addition to concerns regarding the feasibility of medical research, fears of 'blood-stealing' and 'blood-selling' have ethical implications related to cultural sensitivity and informed consent. This study explores anxieties around blood-taking during a malaria treatment trial in the Gambia...
2016: PloS One
Suk Hee Kim, Seong Hee Kang, Bo Sun Kang
BACKGROUND/OBJECTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM)...
August 2016: Nutrition Research and Practice
Renyu Lin, Ziheng Zhang, Lingfeng Chen, Yunfang Zhou, Peng Zou, Chen Feng, Li Wang, Guang Liang
Head and neck cancer is the sixth most common cancer worldwide. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, exhibits a wide range of biological roles including a highly efficient and specific anti-tumor activity. Here, we aimed to examine the effect of DHA on head and neck carcinoma cells and elucidate the potential mechanisms. We used five head and neck carcinoma cell lines and two non-tumorigenic normal epithelial cell lines to achieve our goals. Cells were exposed to DHA and subjected to cellular activity assays including viability, cell cycle analysis, cell death, and angiogenic phenotype...
October 10, 2016: Cancer Letters
Nonkululeko H Zuma, Frans J Smit, Carmen de Kock, Jill Combrinck, Peter J Smith, David D N'Da
In an attempt to improve the efficacy and stability of current, clinically used artemisinins, a series non-hemiacetal ester derivatives of artemisinin were synthesized and evaluated for their in vitro antiplasmodial and anticancer activities as well as cytotoxicities. These esters were synthesized through the reaction of acid anhydrides, or acid chlorides with artemisinin derived alcohol. In vitro antiplasmodial activity assessments were conducted against intraerythrocytic NF54 and Dd2 Plasmodium falciparum strains...
October 21, 2016: European Journal of Medicinal Chemistry
Noemí Bahamontes-Rosa, María G Gomez-Lorenzo, Joël Lelièvre, Ane Rodriguez Alejandre, María Jesus Almela, Sonia Lozano, Esperanza Herreros, Francisco-Javier Gamo
BACKGROUND: Drugs that kill or inhibit Plasmodium gametocytes in the human host could potentially synergize the impact of other chemotherapeutic interventions by blocking transmission. To develop such agents, reliable methods are needed to study the in vitro activity of compounds against gametocytes. This study describes a novel assay for characterizing the activity of anti-malarial drugs against the later stages of Plasmodium falciparum gametocyte development using real-time PCR (qPCR)...
2016: Malaria Journal
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