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Primaquine

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https://www.readbyqxmd.com/read/27923405/cytochrome-p450-2d-mediated-metabolism-is-not-necessary-for-tafenoquine-and-primaquine-to-eradicate-the-erythrocytic-stages-of-plasmodium-berghei
#1
Erin E Milner, Jonathan Berman, Diana Caridha, Samuel P Dickson, Mark Hickman, Patricia J Lee, Sean R Marcsisin, Lisa T Read, Norma Roncal, Brian A Vesely, Lisa H Xie, Jing Zhang, Ping Zhang, Qigui Li
BACKGROUND: Due to the ability of the 8-aminoquinolines (8AQs) to kill different stages of the malaria parasite, primaquine (PQ) and tafenoquine (TQ) are vital for causal prophylaxis and the eradication of erythrocytic Plasmodium sp. parasites. Recognizing the potential role of cytochrome (CYP) 450 2D6 in the metabolism and subsequent hepatic efficacy of 8-aminoquinolines, studies were designed to explore whether CYP2D-mediated metabolism was related to the ability of single-dose PQ and TQ to eliminate the asexual and sexual erythrocytic stages of Plasmodium berghei...
December 7, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27916811/design-synthesis-and-biological-evaluation-of-novel-primaquine-cinnamic-acid-conjugates-of-the-amide-and-acylsemicarbazide-type
#2
Kristina Pavić, Ivana Perković, Petra Gilja, Filip Kozlina, Katja Ester, Marijeta Kralj, Dominique Schols, Dimitra Hadjipavlou-Litina, Eleni Pontiki, Branka Zorc
In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a-k) or via a spacer (compounds 7a-k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a-k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B)...
November 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27905633/-failure-to-radical-cure-in-plasmodium-vivax-malaria
#3
Julián García, Agustín Seijo, Andrés Benchetrit, Esteban Couto, Sofía Echazarreta, Susana Lloveras, Tomás Orduna
Relapsing Plasmodium vivax malaria is due to activation of dormant intrahepatic parasitic forms known as hypnozoits. Primaquine is the only available drug effective against hypnozoits and, alongside a schizonticidal drug, constitutes the radical treatment of malaria. Failure of radical treatment is frequently attributed to inadequate dosing, poor adherence, or reinfection. However, several cases of radical treatment failure without these factors have been reported, inferring that metabolic properties of the host or tolerance mechanisms of the parasite may be implied...
August 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/27880809/molecular-analysis-of-glucose-6-phosphate-dehydrogenase-gene-mutations-in-bangladeshi-individuals
#4
Suprovath Kumar Sarker, Md Tarikul Islam, Grace Eckhoff, Mohammad Amir Hossain, Syeda Kashfi Qadri, A K M Muraduzzaman, Golam Sarower Bhuyan, Mohammod Shahidullah, Mohammad Abdul Mannan, Sarabon Tahura, Manzoor Hussain, Shahida Akhter, Nazmun Nahar, Tahmina Shirin, Firdausi Qadri, Kaiissar Mannoor
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations...
2016: PloS One
https://www.readbyqxmd.com/read/27825738/the-gametocytocidal-efficacy-of-different-single-doses-of-primaquine-with-dihydroartemisinin-piperaquine-in-asymptomatic-parasite-carriers-in-the-gambia-a-randomized-controlled-trial
#5
Joseph Okebe, Teun Bousema, Muna Affara, Gian Luca Di Tanna, Edgard Dabira, Abdoulaye Gaye, Frank Sanya-Isijola, Henry Badji, Simon Correa, Davis Nwakanma, Jean-Pierre Van Geertruyden, Chris Drakeley, Umberto D'Alessandro
BACKGROUND: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown. METHODS: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0...
October 23, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27821127/treatment-seeking-behaviour-and-associated-costs-for-malaria-in-papua-indonesia
#6
Muhammad Karyana, Angela Devine, Enny Kenangalem, Lenny Burdarm, Jeanne Rini Poespoprodjo, Ram Vemuri, Nicholas M Anstey, Emiliana Tjitra, Ric N Price, Shunmay Yeung
BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27799639/epidemiology-of-plasmodium-vivax-malaria-in-peru
#7
Angel Rosas-Aguirre, Dionicia Gamboa, Paulo Manrique, Jan E Conn, Marta Moreno, Andres G Lescano, Juan F Sanchez, Hugo Rodriguez, Hermann Silva, Alejandro Llanos-Cuentas, Joseph M Vinetz
Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P...
October 31, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27799636/implications-of-plasmodium-vivax-biology-for-control-elimination-and-research
#8
Piero L Olliaro, John W Barnwell, Alyssa Barry, Kamini Mendis, Ivo Mueller, John C Reeder, G Dennis Shanks, Georges Snounou, Chansuda Wongsrichanalai
This paper summarizes our current understanding of the biology of Plasmodium vivax, how it differs from Plasmodium falciparum, and how these differences explain the need for P. vivax-tailored interventions. The article further pinpoints knowledge gaps where investments in research are needed to help identify and develop such specific interventions. The principal obstacles to reduce and eventually eliminate P. vivax reside in 1) its higher vectorial capacity compared with P. falciparum due to its ability to develop at lower temperature and over a shorter sporogonic cycle in the vector, allowing transmission in temperate zones and making it less sensitive to vector control measures that are otherwise effective on P...
October 31, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27793909/attenuation-of-colchicine-toxicity-in-drug-resistant-cancer-cells-by-co-treatment-with-anti-malarial-drugs
#9
Ae-Ran Choi, Ju-Hwa Kim, Ji Hyun Cheon, Hyung Sik Kim, Sungpil Yoon
BACKGROUND/AIM: Colchicine (COL) is a well-known and potent microtubule targeting anticancer agent. The purpose of our study was to identify conditions that increase sensitization of COL-resistant cancer cells that overexpress P-glycoprotein (P-gp). MATERIALS AND METHODS: The anti-malarial drugs chloroquine (CHL), mefloquine (MEF) and primaquine (PRI) have been shown to increase sensitization in drug-resistant KBV20C cells via P-gp inhibition. Therefore, we tested whether co-treatment of COL with PRI, CHL or MEF increases sensitivity in COL-resistant KBV20C cells over that of cells treated with COL alone and whether these effects are attributable to P-gp activity...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27784313/an-optimised-age-based-dosing-regimen-for-single-low-dose-primaquine-for-blocking-malaria-transmission-in-cambodia
#10
Rithea Leang, Naw Htee Khu, Mavuto Mukaka, Mark Debackere, Rupam Tripura, Soy Ty Kheang, Say Chy, Neeraj Kak, Philippe Buchy, Arnaud Tarantola, Didier Menard, Arantxa Roca-Felterer, Rick M Fairhurst, Sim Kheng, Sinoun Muth, Song Ngak, Arjen M Dondorp, Nicholas J White, Walter Robert John Taylor
BACKGROUND: In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P...
October 27, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27779751/distinct-subcellular-mechanisms-for-the-enhancement-of-the-surface-membrane-expression-of-sk2-channel-by-its-interacting-proteins-%C3%AE-actinin2-and-filamin-a
#11
Zheng Zhang, Hannah A Ledford, Seojin Park, Wenying Wang, Sassan Rafizadeh, Hyo Jeong Kim, Wilson Xu, Ling Lu, Victor C Lau, Anne A Knowlton, Xiao-Dong Zhang, Ebenezer N Yamoah, Nipavan Chiamvimonvat
The normal function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane. Small-conductance, Ca(2+) -activated K(+) channels (SK, KCa 2) are expressed in human atrial myocytes and responsible for shaping atrial action potentials. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. We have previously demonstrated that the C and N termini of SK2 channels interact with actin-binding proteins, α-actinin2 and filamin A, respectively...
October 25, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27767381/the-effect-of-snps-in-cyp450-in-chloroquine-primaquine-plasmodium-vivax-malaria-treatment
#12
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria DO Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27731362/a-humanized-mouse-model-for-sequestration-of-plasmodium-falciparum-sexual-stages-and-in-vivo-evaluation-of-gametocytidal-drugs
#13
Yoann Duffier, Audrey Lorthiois, Pau Cisteró, Florian Dupuy, Grégory Jouvion, Laurence Fiette, Dominique Mazier, Alfredo Mayor, Catherine Lavazec, Alicia Moreno Sabater
The development of new drugs to disrupt malaria transmission requires the establishment of an in vivo model to address the biology of Plasmodium falciparum sexual stages (gametocytes). Herein we show that chemically immune-modulated NSG mice grafted with human erythrocytes support complete sexual development of P. falciparum parasites and generate high gametocytemia. Immunohistochemistry and RT-qPCR analyses indicate an enrichment of immature gametocytes in the bone marrow and the spleen, suggesting a sequestration mechanism reminiscent to that observed in humans...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27708189/epidemiology-and-control-of-plasmodium-vivax-in-afghanistan
#14
Toby Leslie, Sami Nahzat, Walid Sediqi
Around half of the population of Afghanistan resides in areas at risk of malaria transmission. Two species of malaria (Plasmodium vivax and Plasmodium falciparum) account for a high burden of disease-in 2011, there were more than 300,000 confirmed cases. Around 80-95% of malaria is P. vivax Transmission is seasonal and focal, below 2,000 m in altitude, and in irrigated areas which allow breeding of anopheline mosquito vectors. Malaria risk is stratified to improve targeting of interventions. Sixty-three of 400 districts account for ∼85% of cases, and are the target of more intense control efforts...
October 5, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27708185/epidemiology-of-plasmodium-vivax-in-indonesia
#15
Claudia Surjadjaja, Asik Surya, J Kevin Baird
Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients...
October 5, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27677694/the-acceptability-of-mass-administrations-of-anti-malarial-drugs-as-part-of-targeted-malaria-elimination-in-villages-along-the-thai-myanmar-border
#16
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
https://www.readbyqxmd.com/read/27672207/screening-for-glucose-6-phosphate-dehydrogenase-deficiency-using-three-detection-methods-a-cross-sectional-survey-in-southwestern-uganda
#17
Michelle E Roh, Caesar Oyet, Patrick Orikiriza, Martina Wade, Juliet Mwanga-Amumpaire, Yap Boum, Gertrude N Kiwanuka, Sunil Parikh
Despite the potential benefit of primaquine in reducing Plasmodium falciparum transmission and radical cure of Plasmodium vivax and Plasmodium ovale infections, concerns over risk of hemolytic toxicity in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd) have hampered its deployment. A cross-sectional survey was conducted in 2014 to assess the G6PDd prevalence among 631 children between 6 and 59 months of age in southwestern Uganda, an area where primaquine may be a promising control measure...
November 2, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27639847/safety-efficacy-and-pharmacokinetic-evaluations-of-a-new-coated-chloroquine-tablet-in-a-single-arm-open-label-non-comparative-trial-in-brazil-a-step-towards-a-user-friendly-malaria-vivax-treatment
#18
Dhelio Pereira, André Daher, Graziela Zanini, Ivan Maia, Lais Fonseca, Luciana Pitta, Rosilene Ruffato, Paola Marchesini, Cor Jesus Fontes
BACKGROUND: Malaria remains a major public health problem, with half the world population at risk of contracting malaria. The effects of Plasmodium vivax on prosperity and longevity have been highlighted in several recent clinical case reports. The first line of vivax treatment drugs has seen no radical innovation for more than 60 years. This study introduces a subtle incremental innovation to vivax treatment: a chloroquine and primaquine co-blister. The co-blister includes a new chloroquine formulation incorporating coated tablets to mask the drug's bitter taste and user-friendly packaging containing tablets of each drug, which may improve patient adherence and facilitate the appropriate use of the drugs...
2016: Malaria Journal
https://www.readbyqxmd.com/read/27618912/pathway-specific-inhibition-of-primaquine-metabolism-by-chloroquine-quinine
#19
Pius S Fasinu, Babu L Tekwani, Bharathi Avula, Narayan D Chaurasiya, N P Dhammika Nanayakkara, Yan-Hong Wang, Ikhlas A Khan, Larry A Walker
BACKGROUND: There has been some evidence to suggest that the addition of chloroquine (CQ) or quinine (QN) to 8-aminoquinoline (8-AQ) treatment regimens may increase the therapeutic efficacy of the 8-AQ and simultaneously mitigate against its haemolytic toxicity. However, both CQ and QN are considered effective, although perhaps moderate inhibitors of CYP2D6, an enzyme now regarded as necessary for primaquine (PQ) pharmacologic activity. An understanding of the influence of CQ and QN on the metabolism of PQ may shed light on the potential mechanisms of the beneficial interaction...
2016: Malaria Journal
https://www.readbyqxmd.com/read/27614409/novel-urea-and-bis-urea-primaquine-derivatives-with-hydroxyphenyl-or-halogenphenyl-substituents-synthesis-and-biological-evaluation
#20
I Perković, M Antunović, I Marijanović, K Pavić, K Ester, M Kralj, J Vlainić, I Kosalec, D Schols, D Hadjipavlou-Litina, E Pontiki, B Zorc
A series of novel compounds 3a-j and 6a-j with primaquine and hydroxyl or halogen substituted benzene moieties bridged by urea or bis-urea functionalities were designed, synthesized and evaluated for biological activity. The title compounds were prepared using benzotriazole as the synthon, through several synthetic steps. 3-[3,5-Bis(trifluoromethyl)phenyl]-1-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}urea (3j) was the most active urea and 1-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-3-[3-(trifluoromethyl)phenyl]urea (6h) the most active bis-urea derivative in antiproliferative screening in vitro against eight tested cancer cell lines...
August 24, 2016: European Journal of Medicinal Chemistry
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