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https://www.readbyqxmd.com/read/28938592/visible-light-sensitive-titanium-dioxide-nanoplatform-for-tumor-responsive-fe2-liberating-and-artemisinin-delivery
#1
Huijuan Zhang, Hongling Zhang, Xing Zhu, Xiaoge Zhang, Qianqian Chen, Jianjiao Chen, Lin Hou, Zhenzhong Zhang
Artemisinin is a kind of Fe(2+)-dependent drugs. Artemisinin and Fe(2+) co-transport systems can improve its anti-tumor effect. In this study, a visible light-sensitive nanoplatform (HA-TiO2-IONPs/ART) was developed. Detailed investigation demonstrated that HA-TiO2-IONPs/ART could realize Fe(2+) and artemisinin synchronous co-delivery and tumor-responsive release. This feature enhanced the anti-tumor efficiency of artemisinin significantly. In vitro results proved that hyaluronic acid modification could improve the biocompatibility, dispersion stability and cytophagy ability of nanocarriers...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935919/split-dosing-of-artemisinins-does-not-improve-antimalarial-therapeutic-efficacy
#2
N J White, J Watson, E A Ashley
It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934435/declining-transmission-and-immunity-to-malaria-and-emerging-artemisinin-resistance-in-thailand-a-longitudinal-study
#3
Ricardo Ataíde, Rosanna Powell, Kerryn Moore, Alistair McLean, Aung Pyae Phyo, Shalini Nair, Marina White, Tim J Anderson, James G Beeson, Julie A Simpson, Francois Nosten, Freya J I Fowkes
Background: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. Methods: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28927405/the-use-of-respondent-driven-sampling-to-assess-malaria-knowledge-treatment-seeking-behaviours-and-preventive-practices-among-mobile-and-migrant-populations-in-a-setting-of-artemisinin-resistance-in-western-cambodia
#4
Po Ly, Julie Thwing, Colleen McGinn, Cesia E Quintero, Narann Top-Samphor, Najibullah Habib, Jack S Richards, Sara E Canavati, Seshu Babu Vinjamuri, Chea Nguon
BACKGROUND: Multi-drug-resistant Plasmodium falciparum threatens malaria elimination efforts in Cambodia and the Greater Mekong Subregion (GMS). Malaria burden in the GMS is higher among certain high-risk demographic groups in Cambodia, especially among migrant and mobile populations (MMPs). This respondent driven sampling (RDS) study was conducted in order to determine malaria knowledge, treatment-seeking behaviours and preventive practices among two MMP groups in Western Cambodia. METHODS: An RDS survey of MMPs was implemented in four purposively-selected communes along the Thai-Cambodia border; two in Veal Veang District and two in Pailin Province, chosen due to their sizeable MMP groups, their convenience of access, and their proximity to Thailand, which allowed for comparison with RDS studies in Thailand...
September 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28923866/changing-antimalarial-drug-sensitivities-in-uganda
#5
Stephanie A Rasmussen, Frida G Ceja, Melissa D Conrad, Patrick K Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Samuel L Nsobya, Philip J Rosenthal, Roland A Cooper
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28903759/knowledge-access-and-utilization-of-bed-nets-among-stable-and-seasonal-migrants-in-an-artemisinin-resistance-containment-area-of-myanmar
#6
Wint Phyo Than, Tin Oo, Khin Thet Wai, Aung Thi, Philip Owiti, Binay Kumar, Hemant Deepak Shewade, Rony Zachariah
BACKGROUND: Myanmar lies in the Greater Mekong sub-region of South-East Asia faced with the challenge of emerging resistance to artemisinin combination therapies (ACT). Migrant populations are more likely than others to spread ACT resistance. A vital intervention to reduce malaria transmission, resistance spread and eliminate malaria is the use of bed nets. Among seasonal and stable migrants in an artemisinin resistance containment region of Myanmar, we compared a) their household characteristics, b) contact with health workers and information material, and c) household knowledge, access and utilization of bed nets...
September 14, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28903755/prevalence-of-k13-mutation-and-day-3-positive-parasitaemia-in-artemisinin-resistant-malaria-endemic-area-of-cambodia-a-cross-sectional-study
#7
Soy Ty Kheang, Siv Sovannaroth, Sovann Ek, Say Chy, Phally Chhun, Sokkieng Mao, Sokomar Nguon, Dy Soley Lek, Didier Menard, Neeraj Kak
BACKGROUND: The presence of artemisinin-resistant malaria parasites was confirmed in western Cambodia in 2009. In 2013, mutations in the propeller domain of the kelch protein K13 was found to be associated with artemisinin resistance. A cross-sectional study was conducted to determine the prevalence of Day-3 parasitaemia, estimate the frequency of k13 molecular marker and assess their relationship in the context of operational research. METHODS: Blood smears and filter paper blood spots were collected from febrile patients in Kravanh District, Pursat Province...
September 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28902565/molecular-cloning-and-characterization-of-ribosomal-protein-s9-in-echinococcus-granulosus
#8
Limei Wen, Guodong Lü, Shuai Lu, Huijing Gao, Bei Chen, Yunfang Ma, Yuan Yuan, Haibo Zhang, Yunfeng Xiao, Hui Liu, Jun Zhao, Jianhua Wang
Ribosomal protein S9 (RPS9) is an essential functional gene that participate in DNA repair and developmental regulations. A sequence homolog of RPS9 has been found to be upregulated in the protoscoleces (PSCs) of Echinococcus granulosus treated with artemisinin (ART). However, Echinococcus granulosus RPS9 (EgRPS9) has not been identified before. In the present study, the 657 bp cDNA encoding EgRPS9 was cloned. Amino acid sequence analysis showed that EgRPS9 was similar to the RSP9 proteins from Schistosoma japonicum (SjRPS9, 86 %) and Schistosoma mansoni (SmRPS9, 79 %)...
September 13, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28895080/population-pharmacokinetic-and-pharmacodynamic-modeling-of-artemisinin-resistance-in-southeast-asia
#9
Jesmin Lohy Das, Arjen M Dondorp, Francois Nosten, Aung Pyae Phyo, Warunee Hanpithakpong, Pascal Ringwald, Pharath Lim, Nicholas J White, Mats O Karlsson, Martin Bergstrand, Joel Tarning
Orally administered artemisinin-based combination therapy is the first-line treatment against uncomplicated P. falciparum malaria worldwide. However, the increasing prevalence of artemisinin resistance is threatening efforts to treat and eliminate malaria in Southeast Asia. This study aimed to characterize the exposure-response relationship of artesunate in patients with artemisinin sensitive and resistant malaria infections. Patients were recruited in Pailin, Cambodia (n = 39), and Wang Pha, Thailand (n = 40), and received either 2 mg/kg/day of artesunate mono-therapy for 7 consecutive days or 4 mg/kg/day of artesunate monotherapy for 3 consecutive days followed by mefloquine 15 and 10 mg/kg for 2 consecutive days...
September 11, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28893264/maximizing-research-study-effectiveness-in-malaria-elimination-settings-a-mixed-methods-study-to-capture-the-experiences-of-field-based-staff
#10
Sara E Canavati, Cesia E Quintero, Britt Haller, Dysoley Lek, Sovann Yok, Jack S Richards, Maxine Anne Whittaker
BACKGROUND: In a drug-resistant, malaria elimination setting like Western Cambodia, field research is essential for the development of novel anti-malarial regimens and the public health solutions necessary to monitor the spread of resistance and eliminate infection. Such field studies often face a variety of similar implementation challenges, but these are rarely captured in a systematic way or used to optimize future study designs that might overcome similar challenges. Field-based research staff often have extensive experience and can provide valuable insight regarding these issues, but their perspectives and experiences are rarely documented and seldom integrated into future research protocols...
September 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28893243/impact-of-pharmacy-worker-training-and-deployment-on-access-to-essential-medicines-for-children-under-five-in-malawi-a-cluster-quasi-experimental-evaluation
#11
Joseph B Babigumira, Solomon J Lubinga, Alisa M Jenny, Erin Larsen-Cooper, Jessica Crawford, Charles Matemba, Andy Stergachis
BACKGROUND: Poor access to essential medicines is common in many low- and middle-income countries, partly due to an insufficient and inadequately trained workforce to manage the medicines supply chain. We conducted a prospective impact evaluation of the training and deployment of pharmacy assistants (PAs) to rural health centers in Malawi. METHODS: A quasi-experimental design was used to compare access to medicines in two districts where newly trained PAs were deployed to health centers (intervention) and two districts with no trained PAs at health centers (comparison)...
September 11, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28890548/water-soluble-artemisinin-derivatives-as-promising-therapeutic-immunosuppressants-of-autoimmune-diseases
#12
Heng Li, Jianping Zuo, Wei Tang
No abstract text is available yet for this article.
September 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28887771/antimalarial-drugs-available-in-the-city-cabinda-angola-in-2016
#13
M Muila, P Gazin
Antimalarial drug offerings in the city of Cabinda (Angola) were assessed during the fourth quarter of 2016. Combinations of artemisinin with other effective antimalarial drugs were available free of charge in public health centres, theoretically after a biological validation of the diagnosis of a malaria attack. Private pharmacies offered many products without medical prescription, most of them being ACT (Artemisinin Combined Therapy) but some being Artemisia derivatives alone. The cost of treatment for a presumptive attack varied from 14 to 44 €...
September 8, 2017: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/28886522/quantification-of-the-antimalarial-drug-pyronaridine-in-whole-blood-using-lc-ms-ms-increased-sensitivity-resulting-from-reduced-non-specific-binding
#14
Daniel Blessborn, Karnrawee Kaewkhao, Lijiang Song, Nicholas J White, Nicholas P J Day, Joel Tarning
Malaria is one of the most important parasitic diseases of man. The development of drug resistance in malaria parasites is an inevitable consequence of their widespread and often unregulated use. There is an urgent need for new and effective drugs. Pyronaridine is a known antimalarial drug that has received renewed interest as a partner drug in artemisinin-based combination therapy. To study its pharmacokinetic properties, particularly in field settings, it is necessary to develop and validate a robust, highly sensitive and accurate bioanalytical method for drug measurements in biological samples...
August 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28880869/differences-in-chemical-constituents-of-artemisia-annua-l-from-different-geographical-regions-in-china
#15
Xiaobo Zhang, Yuping Zhao, Lanping Guo, Zhidong Qiu, Luqi Huang, Xiaobo Qu
BACKGROUND: Daodi-herb is a part of Chinese culture, which has been naturally selected by traditional Chinese medicine clinical practice for many years. Sweet wormwood herb is a kind of Daodi-herb, and comes from Artemisia annua L. Artemisinin is a kind of effective antimalarial drug being extracted from A. annua. Because of artemisinin, Sweet wormwood herb earns a reputation. Based on the Pharmacopoeia of the People's Republic of China (PPRC), Sweet wormwood herb can be used to resolve summerheat-heat, and prevent malaria...
2017: PloS One
https://www.readbyqxmd.com/read/28875841/new-molecular-targets-and-strategies-for-antimalarial-discovery
#16
Anna Caroline Aguiar, Lorena R F de Sousa, Celia R S Garcia, Glaucius Oliva, Rafael V C Guido
Malaria remains a major health problem, especially because of the emergence of resistant P. falciparum strains to artemisinin derivatives. In this context, safe and affordable antimalarial drugs are desperately needed. New proteins have been investigated as molecular targets for research and development of innovative compounds with well-defined mechanism of action. In this review, we highlight genetically and clinically validated plasmodial proteins as drug targets for the next generation of therapeutics. The enzymes described herein are involved in hemoglobin hydrolysis, the invasion process, elongation factors for protein synthesis, pyrimidine biosynthesis, post-translational modifications such as prenylation, phosphorylation and histone acetylation, generation of ATP in mitochondrial metabolism and aminoacylation of RNAs...
August 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28874682/hydrogen-peroxide-dynamics-in-subcellular-compartments-of-malaria-parasites-using-genetically-encoded-redox-probes
#17
Mahsa Rahbari, Stefan Rahlfs, Jude M Przyborski, Anna Katharina Schuh, Nicholas H Hunt, David A Fidock, Georges E Grau, Katja Becker
Redox balance is essential for the survival, growth and multiplication of malaria parasites and oxidative stress is involved in the mechanism of action of many antimalarial drugs. Hydrogen peroxide (H2O2) plays an important role in redox signalling and pathogen-host cell interactions. For monitoring intra- and subcellular redox events, highly sensitive and specific probes are required. Here, we stably expressed the ratiometric H2O2 redox sensor roGFP2-Orp1 in the cytosol and the mitochondria of Plasmodium falciparum (P...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28864166/artemisinin-permeability-via-caco-2-cells-increases-after-simulated-digestion-of-artemisia-annua-leaves
#18
Matthew R Desrosiers, Pamela J Weathers
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua has been used for > 2000yrs to treat fever and is more recently known for producing the important antimalarial drug, artemisinin. AIM OF THE STUDY: Artemisinin combination therapies (ACTs) are effective for treating malaria, but are often unavailable to those in need. Dried leaves of A. annua (DLA) have recently been studied as a cost effective alternative to traditional ACTs. DLA was shown to dramatically increase oral bioavailability compared to pure artemisinin, so more investigation into the mechanisms causing this increased bioavailability is needed...
August 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28864033/characterising-the-effect-of-antimalarial-drugs-on-the-maturation-and-clearance-of-murine-blood-stage-plasmodium-parasites-in-vivo
#19
David S Khoury, Deborah Cromer, Trish Elliott, Megan S F Soon, Bryce S Thomas, Kylie R James, Shannon E Best, Rosemary A Aogo, Jessica A Engel, Kate H Gartlan, Jasmin Akter, Ismail Sebina, Ashraful Haque, Miles P Davenport
The artemisinins are the first-line therapy for severe and uncomplicated malaria, since they cause rapid declines in parasitemia after treatment. Despite this, in vivo mechanisms underlying this rapid decline remain poorly characterised. The overall decline in parasitemia is the net effect of drug inhibition of parasites and host clearance, which competes against any ongoing parasite proliferation. Separating these mechanisms in vivo was not possible through measurements of total parasitemia alone. Therefore, we employed an adoptive transfer approach in which C57BL/6J mice were transfused with Plasmodium berghei ANKA strain-infected, fluorescent red blood cells, and subsequently drug-treated...
August 31, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28861412/stable-production-of-the-antimalarial-drug-artemisinin-in-the-moss-physcomitrella-patens
#20
Nur Kusaira Binti Khairul Ikram, Arman Beyraghdar Kashkooli, Anantha Vithakshana Peramuna, Alexander R van der Krol, Harro Bouwmeester, Henrik Toft Simonsen
Malaria is a real and constant danger to nearly half of the world's population of 7.4 billion people. In 2015, 212 million cases were reported along with 429,000 estimated deaths. The World Health Organization recommends artemisinin-based combinatorial therapies, and the artemisinin for this purpose is mainly isolated from the plant Artemisia annua. However, the plant supply of artemisinin is irregular, leading to fluctuation in prices. Here, we report the development of a simple, sustainable, and scalable production platform of artemisinin...
2017: Frontiers in Bioengineering and Biotechnology
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